Diferenças do Desenvolvimento Sexual em pessoas com o conjunto de cromossomos 46,XY.
Introdução
O que você precisa saber de cara
Diferenças do Desenvolvimento Sexual em pessoas com o conjunto de cromossomos 46,XY.
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 228 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 495 características clínicas mais associadas, ordenadas por frequência.
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
24 genes identificados com associação a esta condição.
Converts testosterone (T) into 5-alpha-dihydrotestosterone (DHT) and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology
Microsome membraneEndoplasmic reticulum membrane
Pseudovaginal perineoscrotal hypospadias
A form of male pseudohermaphroditism in which 46,XY males show ambiguous genitalia at birth, including perineal hypospadias and a blind perineal pouch, and develop masculinization at puberty. The name of the disorder stems from the finding of a blind-ending perineal opening resembling a vagina and a severely hypospadiac penis with the urethra opening onto the perineum.
ATP-binding RNA helicase that plays a role in maturation of the small ribosomal subunit in ribosome biogenesis (PubMed:30582406). Required for the release of the U3 snoRNP from pre-ribosomal particles (PubMed:30582406). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and wor
Nucleus, nucleolusCytoplasmNucleus membrane
Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies
An autosomal recessive neurodevelopmental disorder characterized by severe developmental delay, impaired intellectual development, hypotonia, brain anomalies including cortical volume loss, corpus callosum dysgenesis and cerebellar hypoplasia, and variable dysmorphic features. Patients may have platyspondyly, scoliosis, and cardiac anomalies.
Putative oxidoreductase. Acts as a tumor suppressor and plays a role in apoptosis. Required for normal bone development (By similarity). May function synergistically with p53/TP53 to control genotoxic stress-induced cell death. Plays a role in TGFB1 signaling and TGFB1-mediated cell death. May also play a role in tumor necrosis factor (TNF)-mediated cell death. Inhibits Wnt signaling, probably by sequestering DVL2 in the cytoplasm
CytoplasmNucleusMitochondrionGolgi apparatusLysosome
Involved in the targeting and/or fusion of transport vesicles to their target membrane during transport of proteins from the early endosome to the lysosome. Required for heterotypic fusion of late endosomes with lysosomes and homotypic lysosomal fusion. Required for calcium regulated lysosomal exocytosis. Involved in the export of chylomicrons from the endoplasmic reticulum to the cis Golgi. Required for exocytosis of mediators during eosinophil and neutrophil degranulation, and target cell kill
Cytoplasmic vesicle, secretory vesicle membraneGolgi apparatus, trans-Golgi network membraneLate endosome membraneLysosome membraneEndoplasmic reticulum membraneCytoplasmic vesicle, phagosome membraneSynapse, synaptosome
Lipid phosphatase which dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) (PubMed:10900271, PubMed:11001925, PubMed:12646134, PubMed:14722070). Has also been shown to dephosphorylate phosphotyrosine- and phosphoserine-containing peptides (PubMed:9537414). Negatively regulates EGFR degradation through regulation of EGFR trafficking from the late endosome to the lysosome (PubMed:14722070). Plays a role in vacuolar formation and morph
CytoplasmCell membraneCell projection, filopodiumCell projection, ruffleLate endosomeCytoplasm, myofibril, sarcomere
Myopathy, centronuclear, X-linked
A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.
Transcriptional regulator that controls a genetic switch in male development (PubMed:11563911). It is necessary and sufficient for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells (PubMed:16414182, PubMed:16996051). Involved in different aspects of gene regulation including promoter activation or repression (PubMed:9525897). Binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3' (PubMed:115639
Nucleus speckleCytoplasmNucleus
46,XY sex reversal 1
A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype. Patients manifest rapid and early degeneration of their gonads, which are present in the adult as 'streak gonads', consisting mainly of fibrous tissue and variable amounts of ovarian stroma. As a result these patients do not develop secondary sexual characteristics at puberty. The external genitalia in these subjects are completely female, and Muellerian structures are normal.
Transactivates the HES3 promoter independently of NOTCH proteins. HES3 is a non-canonical NOTCH target gene which lacks binding sites for RBPJ
Nucleus
Hypospadias 2, X-linked
A common malformation in which the urethra opens on the ventral side of the penis, due to developmental arrest of urethral fusion. The opening can be located glandular, penile, or even more posterior in the scrotum or perineum. Hypospadias is a feature of several syndromic disorders, including the androgen insensitivity syndrome and Opitz syndrome.
Important signaling molecule that activates signaling cascades downstream of NTRK2 (PubMed:11152678). During development, promotes the survival and differentiation of selected neuronal populations of the peripheral and central nervous systems. Participates in axonal growth, pathfinding and in the modulation of dendritic growth and morphology. Major regulator of synaptic transmission and plasticity at adult synapses in many regions of the CNS. The versatility of BDNF is emphasized by its contribu
Secreted
May regulate MCM3AP phosphorylation through phosphatase recruitment (By similarity). May act as a negative regulator of ABCB1 expression and function through the dephosphorylation of ABCB1 by TFPI2/PPP2R3C complex (PubMed:24333728). May play a role in the activation-induced cell death of B-cells (By similarity)
NucleusCytoplasm
Myoectodermal gonadal dysgenesis syndrome
An autosomal recessive disorder characterized by 46,XY complete gonadal dysgenesis and extragonadal anomalies, including typical facial gestalt, low birth weight, myopathy, rod and cone dystrophy, anal atresia, omphalocele, sensorineural hearing loss, dry and scaly skin, skeletal abnormalities, renal agenesis and neuromotor delay.
Transcription factor with important functions in the development of the eye, nose, central nervous system and pancreas. Required for the differentiation of pancreatic islet alpha cells (By similarity). Competes with PAX4 in binding to a common element in the glucagon, insulin and somatostatin promoters. Regulates specification of the ventral neuron subtypes by establishing the correct progenitor domains (By similarity). Acts as a transcriptional repressor of NFATC1-mediated gene expression (By s
Nucleus
Aniridia 1
A congenital, bilateral, panocular disorder characterized by complete absence of the iris or extreme iris hypoplasia. Aniridia is not just an isolated defect in iris development but it is associated with macular and optic nerve hypoplasia, cataract, corneal changes, nystagmus. Visual acuity is generally low but is unrelated to the degree of iris hypoplasia. Glaucoma is a secondary problem causing additional visual loss over time.
Transcriptional activator. Essential for sexual differentiation and formation of the primary steroidogenic tissues (PubMed:27378692). Binds to the Ad4 site found in the promoter region of steroidogenic P450 genes such as CYP11A, CYP11B and CYP21B. Also regulates the AMH/Muellerian inhibiting substance gene as well as the AHCH and STAR genes. 5'-YCAAGGYC-3' and 5'-RRAGGTCA-3' are the consensus sequences for the recognition by NR5A1 (PubMed:27378692). The SFPQ-NONO-NR5A1 complex binds to the CYP17
Nucleus
46,XY sex reversal 3
A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype.
Nuclear receptor that lacks a DNA-binding domain and acts as a corepressor that inhibits the transcriptional activity of other nuclear receptors through heterodimeric interactions (PubMed:12482977, PubMed:32433991). Component of a cascade required for the development of the hypothalamic-pituitary-adrenal-gonadal axis (PubMed:7990953, PubMed:8675564). May also have a role in the development of the embryo and in the maintenance of embryonic stem cell pluripotency (By similarity)
NucleusCytoplasm
Adrenal hypoplasia, congenital
A disorder of adrenal gland development characterized by absence of the permanent zone of the adrenal cortex, structural disorganization of the adrenal glands, adrenal insufficiency and profound hormonal deficiencies. AHC patients manifest primary adrenal failure usually in early infancy, and hypogonadotropic hypogonadism leading to absent or incomplete sexual maturation. AHC can be inherited in an X-linked or autosomal recessive pattern.
Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. Catalytic component of the chromatin remodeling
NucleusChromosome, telomereNucleus, PML body
Alpha-thalassemia/impaired intellectual development syndrome, X-linked
A disorder characterized by severe psychomotor retardation, facial dysmorphism, urogenital abnormalities, and alpha-thalassemia. An essential phenotypic trait are hemoglobin H erythrocyte inclusions.
Transcription factor that plays a key role in chondrocytes differentiation and skeletal development (PubMed:24038782). Specifically binds the 5'-ACAAAG-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis, including cartilage matrix protein-coding genes COL2A1, COL4A2, COL9A1, COL11A2 and ACAN, SOX5 and SOX6 (PubMed:8640233). Also binds to some promoter regions (By similarity). Plays a central role in successive steps of chondrocyte
Nucleus
Campomelic dysplasia
A rare, often lethal, osteochondrodysplasia characterized by congenital bowing and angulation of long bones. Other skeletal defects include unusually small scapula, deformed pelvis and spine, and a missing pair of ribs. Craniofacial and ear defects are common. Most patients die soon after birth due to respiratory distress which has been attributed to hypoplasia of the tracheobronchial cartilage and small thoracic cage. Up to two-thirds of affected XY individuals have genital defects or may develop as phenotypic females.
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849). Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Tran
NucleusCytoplasm
Androgen insensitivity syndrome
An X-linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype.
A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones (PubMed:21636783). Catalyzes three sequential oxidation reactions of cholesterol, namely the hydroxylation at C22 followed with the hydroxylation at C20 to yield 20R,22R-hydroxycholesterol that is further cleaved between C20 and C22 to yield the C21-steroid pregnenolone and 4-methylpentanal (PubMed:21636783). Mechanistically, uses molecul
Mitochondrion inner membrane
Adrenal insufficiency, congenital, with 46,XY sex reversal
A rare disorder that can present as acute adrenal insufficiency in infancy or childhood. ACTH and plasma renin activity are elevated and adrenal steroids are inappropriately low or absent; the 46,XY patients have female external genitalia, sometimes with clitoromegaly. The phenotypic spectrum ranges from prematurity, complete underandrogenization, and severe early-onset adrenal failure to term birth with clitoromegaly and later-onset adrenal failure. Patients with congenital adrenal insufficiency do not manifest the massive adrenal enlargement typical of congenital lipoid adrenal hyperplasia.
Transcriptional activator that binds to the consensus sequence 5'-AGATAG-3' and plays a key role in cardiac development and function (PubMed:24000169, PubMed:27984724, PubMed:35182466). In cooperation with TBX5, it binds to cardiac super-enhancers and promotes cardiomyocyte gene expression, while it down-regulates endocardial and endothelial gene expression (PubMed:27984724). Involved in bone morphogenetic protein (BMP)-mediated induction of cardiac-specific gene expression. Binds to BMP respons
Nucleus
Atrial septal defect 2
A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria. Patients show other heart abnormalities including ventricular and atrioventricular septal defects, pulmonary valve thickening or insufficiency of the cardiac valves. The disease is not associated with defects in the cardiac conduction system or non-cardiac abnormalities.
The C-terminal part of the desert hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein into two parts (N-product and C-product) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-product (DHH-N) (By similarity). Both activities occur in the endoplasmic reticulum (By similarity). Once cleaved, the C-product is degraded in t
Cell membraneEndoplasmic reticulum membraneGolgi apparatus membraneSecreted
46,XY gonadal dysgenesis with minifascicular neuropathy
An autosomal recessive disorder characterized by gonadal dysgenesis associated with polyneuropathy. Genital anomalies include the presence of a testis on one side and a streak or an absent gonad at the other, persistence of Muellerian duct structures, and a variable degree of genital ambiguity.
Transcription regulator that plays a central role in heart morphogenesis and development of coronary vessels from epicardium, by regulating genes that are essential during cardiogenesis. Essential cofactor that acts via the formation of a heterodimer with transcription factors of the GATA family GATA4, GATA5 and GATA6. Such heterodimer can both activate or repress transcriptional activity, depending on the cell and promoter context. Also required in gonadal differentiation, possibly be regulatin
Nucleus
Tetralogy of Fallot
A congenital heart anomaly which consists of pulmonary stenosis, ventricular septal defect, dextroposition of the aorta (aorta is on the right side instead of the left) and hypertrophy of the right ventricle. In this condition, blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into the body often causing cyanosis.
Component of a protein kinase signal transduction cascade (PubMed:9808624). Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4 (PubMed:9808624). May phosphorylate the MAPK8/JNK1 kinase (PubMed:17761173). Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathway (PubMed:9808624)
46,XY sex reversal 6
A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females.
Catalyzes the conversion of 17-oxosteroids to 17beta-hydroxysteroids (PubMed:16216911, PubMed:26545797, PubMed:27927697, PubMed:8075637). Favors the reduction of androstenedione to testosterone (PubMed:16216911, PubMed:26545797, PubMed:27927697). Testosterone is the key androgen driving male development and function (PubMed:8075637). Uses NADPH while the two other EDH17B enzymes use NADH (PubMed:16216911, PubMed:26545797, PubMed:8075637). Androgens such as epiandrosterone, dehydroepiandrosterone
Endoplasmic reticulum
Male pseudohermaphrodism with gynecomastia
An autosomal recessive disorder that manifests, in males, as undermasculinization characterized by hypoplastic-to-normal internal genitalia (epididymis, vas deferens, seminal vesicles, and ejaculatory ducts) but female external genitalia and the absence of a prostate. This phenotype is caused by inadequate testicular synthesis of testosterone, which, in turn, results in insufficient formation of dihydrotestosterone in the anlage of the external genitalia and prostate during fetal development. At the expected time of puberty, there is a marked increase in plasma leuteinizing hormone and, consequently, in testicular secretion of androstenedione. Hence, a diagnostic hallmark of this disorder is a decreased plasma testosterone-to-androstenedione ratio. Significant amounts of the circulating androstenedione are, however, converted to testosterone, in peripheral tissues, thereby causing virilization.
Palmitoyl acyltransferase that catalyzes N-terminal palmitoylation of SHH; which is required for SHH signaling (PubMed:18534984, PubMed:24784881, PubMed:31875564). It also catalyzes N-terminal palmitoylation of DHH (PubMed:24784881). Promotes the transfer of palmitoyl-CoA from the cytoplasmic to the luminal side of the endoplasmic reticulum membrane, where SHH palmitoylation occurs (PubMed:31875564). It is an essential factor for proper embryonic development and testicular organogenesis (PubMed:
Endoplasmic reticulum membraneGolgi apparatus membrane
Nivelon-Nivelon-Mabille syndrome
An autosomal recessive syndrome characterized by progressive microcephaly, cerebellar vermis hypoplasia, and skeletal dysplasia. Additional variable features include early infantile-onset seizures, intrauterine and postnatal growth retardation, generalized chondrodysplasia, and micromelia. 46,XY gonadal dysgenesis may be present.
Transcription factor that plays an important role in cellular development and cell survival (PubMed:7862533). Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3' (PubMed:17716689, PubMed:25258363, PubMed:7862533). Regulates the expression of numerous target genes, including EPO. Plays an essential role for development of the urogenital system. It has a tumor suppressor as well as an oncogenic role in tumor formation. Function may be isoform-specific: isoforms lacking the KTS motif may a
NucleusNucleus, nucleolusCytoplasmNucleus speckleNucleus, nucleoplasm
Frasier syndrome
Characterized by a slowly progressing nephropathy leading to renal failure in adolescence or early adulthood, male pseudohermaphroditism, and no Wilms tumor. As for histological findings of the kidneys, focal glomerular sclerosis is often observed. There is phenotypic overlap with Denys-Drash syndrome. Inheritance is autosomal dominant.
Nucleus, nucleolus
Sudden infant death with dysgenesis of the testes syndrome
Autosomal recessive disorder. Affected infants appear normal at birth, develop signs of visceroautonomic dysfunction early in life, and die before 12 months of age of abrupt cardiorespiratory arrest. Features included bradycardia, hypothermia, severe gastroesophageal reflux, laryngospasm, bronchospasm, and abnormal cardiorespiratory patterns during sleep. Genotypic males with SIDDT had fetal testicular dysgenesis and ambiguous genitalia, with findings such as intraabdominal testes, dysplastic testes, deficient fetal testosterone production, fusion and rugation of the gonadal sac, and partial development of the penile shaft. Female sexual development was normal. Affected infants had an unusual staccato cry, similar to the cry of a goat.
Variantes genéticas (ClinVar)
556 variantes patogênicas registradas no ClinVar.
Vias biológicas (Reactome)
85 vias biológicas associadas aos genes desta condição.
Diagnóstico
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Publicações mais relevantes
Identification of Novel and Known Variants in Epigenetic Genes Associated with Syndromic 46,XY Differences of Sex Development among Moroccan Patients.
46,XY differences of sex development (DSD) are conditions with extreme phenotypic and genetic heterogeneity. Therefore, their diagnosis remains a major challenge for both clinicians and geneticists. In this study, we aimed to identify the underlying genetic causes of DSD in a series of 3 Moroccan patients with syndromic 46,XY DSD recruited in the BRO Biobank. Methods: Karyotyping analysis was performed on peripheral blood samples using standard R banding techniques. SRY gene was analyzed using PCR amplification followed by Sanger sequencing. Whole exome sequencing (WES) was performed after unsuccessful conventional genetic analyses. Candidate variants were evaluated by segregation analysis and molecular modeling. WES identified three pathogenic variants in genes encoding various components of the epigenetic machinery: in patient 1, a novel heterozygous frameshift variant c.4072dup (p.Glu1358GlyfsTer29) in the KAT6B gene associated with two clinically distinct syndromes (genitopatellar syndrome and Say-Barber-Biesecker-Young-Simpson syndrome) was detected; in patient 2, we identified a previously reported de novo heterozygous nonsense variant c.12943C>T (p.Gln4315Ter) in KMT2D responsible for Kabuki syndrome; in patient 3, WES revealed a novel heterozygous missense variant c.4056C>G (p.Phe1352Leu) in CHD7 responsible for CHARGE syndrome. We discuss the genotype-phenotype correlation in these syndromic 46,XY DSD and discuss the relevance of the epigenetic genes in sexual development. Our findings highlight the utility of WES in discriminating clinically overlapping syndromic 46,XY DSD to provide an accurate diagnosis, thus allowing better follow-up and appropriate patient management. In addition, our study enriched the mutational spectrum of syndromic 46,XY DSD and confirmed the genotype-phenotype correlations.
Rare phenotypic spectrum of 17β-hydroxysteroid dehydrogenase 3 deficiency: case series from infancy to adolescence.
17β-Hydroxysteroid dehydrogenase 3 (17β-HSD3) deficiency is a rare 46XY disorder of sex development (DSD) of androgen biosynthesis. We aimed to describe the complexities in diagnosis, gender assignment, and the timing of irreversible surgical interventions in 17β-HSD3 deficiency. We described three genetically confirmed cases of 46XY DSD due to 17β-HSD3 deficiency. All of them had female-appearing external genitalia, and the third case had well-developed breasts with clitoromegaly. The biochemical evaluation showed hCG-stimulated T/A ratios of 0.4 and 0.35 in Cases 1 and 2, respectively, and an unstimulated T/A ratio of 0.25 in Case 3. Molecular analysis revealed three different HSD17B3 variants: c.72C>A(p.Cys24Ter), c.764C>T(p.Ser255Leu), and c.607-1G>A(3'splice site) in the respective cases. Despite the female-appearing external genitalia in Case 1, the parents decided to rear the child as male, whereas Cases 2 and 3 retained a female gender identity. The first two cases were advised to have regular follow-up for gender dysphoria, while Case 3 was managed with injectable leuprolide depot and anti-androgens. 17β-HSD3 deficiency remains a challenging 46 XY DSD due to its clinical heterogeneity and diverse molecular spectrum. This report adds to current molecular knowledge by reporting two novel variants in the HSD17B3 gene.
Upstream SOX9 deletion in a 46,XY girl with acampomelic campomelic dysplasia and absent minipuberty.
Campomelic dysplasia (CD) is a rare congenital skeletal dysplasia frequently associated with differences of sex development (DSD). In about 10% of affected individuals, the bowing of the long bones (campomelia) is absent, referred to as acampomelic campomelic dysplasia (ACD). Most patients with ACD carry heterozygous pathogenic variants within the SOX9 coding region or balanced chromosomal rearrangements involving the 17q24 region. A rarer mechanism involves deletions located upstream of the SOX9 gene. Only five ACD cases with upstream deletions of SOX9 have been reported in the medical literature. We report a female patient affected by ACD with Pierre Robin sequence, complete gonadal dysgenesis (CGD), and hypotonia. Genetic testing revealed a de novo 1.671 Mb deletion located 191 kb upstream of the SOX9 gene. This chromosomal aberration represents the second-largest deletion upstream of SOX9 reported to date. In addition, we describe the patient's endocrine profile, which revealed an absent gonadotropin rise during minipuberty, followed by a delayed increase in infancy. This study expands the clinical and molecular spectrum of ACD, enhancing our understanding of genotype-phenotype correlations of this condition. The phenotypic and endocrinological description of the proband may be helpful for clinicians who consult patients with DSD and skeletal dysplasia.
Molecular genetic diagnosis and surgical management in a cohort of children with 46,XY disorders/differences of sex development.
A firm diagnosis revealing the etiology of disorders/differences of sex development (DSD) is most helpful in guiding clinical management. The aim of this study is to investigate molecular genetic diagnoses and surgical treatment in a cohort of children with 46,XY DSD. A retrospective study was conducted on children with 46,XY DSD. They were referred to a tertiary surgical center during the period between 2011 and 2022 and were found to have genetic alterations, which were considered etiologies for their DSD. Data on clinical presentations, sex of rearing, genetic findings, surgical treatment, and comorbidities were collected and reviewed. A total of 21 patients were included in the study: 11 and 10 were reared as male and female, respectively. Genetic alterations were found as the causes for androgen insensitivity syndrome (n = 4), 5-alpha reductase type II deficiency (n = 5), 17-beta hydroxysteroid dehydrogenase III deficiency (n = 1), 17-alpha hydroxylase deficiency (n = 1), and gonadal dysgenesis (n = 10). Of those with gonadal dysgenesis, the genetic alterations were NR5A1 mutation/deletion (n = 3), DMRT1 deletion (n = 4), WT1 mutation (n = 2), and DAX1 duplication (n = 1). A total of 20/21 patients underwent one or more surgical procedures including hypospadias repair (n = 10), gonadectomy (n = 11), gonadal biopsy (n = 4), hernia repair (n = 4), orchidopexy (n = 1), and feminizing genitoplasty (n = 1). A total of 5/21 had germ cell neoplasms in one or both gonads. A total of 8/10 patients with gonadal dysgenesis had comorbidities involving other systems. Of the whole group, seven patients were found to inherit genetic alterations from their parents. Molecular genetic diagnosis enhances the understanding of etiology, improves diagnostic accuracy, and provides precise guidance in the counseling and surgical management of children with 46,XY DSD.
Functional analysis of SRY variants in individuals with 46,XY differences of sex development.
In mammals, male sexual development is initiated by the expression of the Sex-determining-Region-Y (SRY) gene. SRY contains a highly conserved high mobility group (HMG) box essential for DNA binding and activity. Variants in SRY cause Differences of Sex Development (DSD), accounting for 10-15% of 46, XY gonadal dysgenesis cases. Here, we present the functional analysis of five SRY coding variants identified in patients with 46, XY DSD. Four variants (p.Asp58Glu, p.Arg75Lys, p.Met85Thr, and p.Arg86Ter) are located within the HMG box and one variant (p.Tyr198Cysfs∗18) located in the C-terminal domain. We functionally characterise the impact of these variants in vitro, investigating SRY localisation and transactivational activity using SOX9 regulatory elements that are responsive to SRY. We find that three variants (p.Met85Thr, p.Arg86Ter, and p.Tyr198Cysfs∗18) have reduced or abolished transactivational activity suggesting these are pathogenic, with the p.Arg86Ter variant undetectable in our assays and the p.Met85Thr variant exhibiting reduced nuclear localisation. The pathogenic mechanisms underlying reduced activity of the novel elongated p.Tyr198Cysfs∗18 variant is however unclear, although this variant also affected localisation. In contrast, two additional variants (p.Asp58Glu and p.Arg75Lys) had no discernible effects on nuclear localisation or transactivational activity despite in silico analysis predicting impaired DNA binding. Taken together, our data establish the likely pathogenicity of these SRY variants and improve diagnostic certainty for the patients in which they were identified.
Publicações recentes
Close relationship, similar phenotype of GATA4 and NR5A1 mutations: gonadal dysgenesis and puberty development.
Pubertal Development as a Marker of Gonadal Neoplasm in 46XY Complete Gonadal Dysgenesis.
Phenotypic Variation and Pubertal Outcomes in Males and Females With 46,XY Partial Gonadal Dysgenesis.
Functional analysis of SRY variants in individuals with 46,XY differences of sex development.
[Value of the human chorionic gonadotropin stimulation test in the diagnosis of disorder of sexual development in children].
📚 EuropePMC2 artigos no totalmostrando 200
Identification of Novel and Known Variants in Epigenetic Genes Associated with Syndromic 46,XY Differences of Sex Development among Moroccan Patients.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation[Clinical, hormonal and molecular genetic characteristics of 18 cases of disorders of sex development (DSD) 46,XY associated with variants in the SRD5A2 gene].
Problemy endokrinologiiRare phenotypic spectrum of 17β-hydroxysteroid dehydrogenase 3 deficiency: case series from infancy to adolescence.
Journal of pediatric endocrinology & metabolism : JPEMTesticular cytology and semen analysis in 46, XY differences/disorders of sex development (DSD): implications for fertility.
Pediatric surgery internationalClinical Spectrum, Surgical Management, and Outcomes of NR5A1-Related 46,XY Differences of Sex Development: A Narrative Review.
Medicina (Kaunas, Lithuania)Upstream SOX9 deletion in a 46,XY girl with acampomelic campomelic dysplasia and absent minipuberty.
Orphanet journal of rare diseasesMaternal Microchimerism Is Uncommon in Patients with Hypospadias.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationIsodicentric Y chromosome with SRY duplication in a female with complete gonadal dysgenesis.
Molecular cytogeneticsClose relationship, similar phenotype of GATA4 and NR5A1 mutations: gonadal dysgenesis and puberty development.
Journal of endocrinological investigationThe diagnostic value of stimulated androgen ratios in 5-alpha reductase type 2 (SRD5A2) deficiency: a case series and review of the literature.
Journal of pediatric endocrinology & metabolism : JPEMPersistent Müllerian Duct Syndrome and Concurrent Pre-Germ Cell Neoplasia In Situ.
Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology SocietyCase Report: De novo DHX37 mutations in Saudi patients with 46,XY differences of sex development.
Frontiers in endocrinologyExcision versus division of Müllerian duct remnants in male disorders of sexual development and differentiation: a prospective study to generate anatomical assessment criteria.
Pediatric surgery internationalPubertal Development as a Marker of Gonadal Neoplasm in 46XY Complete Gonadal Dysgenesis.
Journal of pediatric and adolescent gynecologyAmplicon-based targeted next-generation sequencing using dried blood spots for 46,XY differences/disorders of sex development: Aiming for diagnosis by minimally invasive testing.
Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric EndocrinologyPrevalence of Differences of Sex Development Among Pediatric Endocrine Care Centers in Switzerland From 2000 to 2019.
Journal of the Endocrine Society46,XY 17 alpha-hydroxylase/17,20 lyase deficiency with breast development: A case report and literature review.
Endocrine journalNovel SOX9 Gene Variant Associated with Campomelic Dysplasia: Effects on Sex Phenotypes.
Journal of clinical research in pediatric endocrinologyCoproporphyrinogen Oxidase Deficiency Causes Primary Adrenal Insufficiency and 46,XY DSD.
The Journal of clinical endocrinology and metabolismEstrogen-secreting testicular tumors in 46,XY female patients with 17α-hydroxylase/17,20-lyase deficiency: two unusual case reports and a review of the literature.
Frontiers in genetics46, XY under-virilization and NR5A1 variants: Monocentric Indian experience and systematic review.
Annales d'endocrinologiePhenotypic Variation and Pubertal Outcomes in Males and Females With 46,XY Partial Gonadal Dysgenesis.
The Journal of clinical endocrinology and metabolismOligogenic analysis across broad phenotypes of 46,XY differences in sex development associated with NR5A1/SF-1 variants: findings from the international SF1next study.
EBioMedicineProfile of DHX37 gene defects in human genetic diseases: 46,XY disorders of sex development.
Frontiers in endocrinologyMicroscopic testicular sperm extraction in 46, XY differences in sex development caused by 5-alpha reductase type 2 deficiency.
Archives of endocrinology and metabolismMolecular genetic diagnosis and surgical management in a cohort of children with 46,XY disorders/differences of sex development.
Frontiers in pediatricsMYRF Variants in Patients With 46,XY Differences/Disorders of Sex Development and Literature Review.
American journal of medical genetics. Part A46, XY Complete Gonadal Dysgenesis (Swyer Syndrome) Presenting as Primary Amenorrhea in a Normomorphic Adult Female From Kakamega, Kenya.
Clinical case reportsFunctional analysis of SRY variants in individuals with 46,XY differences of sex development.
Molecular and cellular endocrinologyGonadal function and pathology in 17beta-HSD 3 and 5alpha-reductase deficiency.
European journal of endocrinologyA novel CUL4B gene variant activating Wnt4/β-catenin signal pathway to karyotype 46, XY female with disorders of sex development.
Biological researchClinical spectrum and molecular basis in 19 Chinese patients with 46, XY disorder of sexual development caused by NR5A1 mutations.
Orphanet journal of rare diseasesGenetic and Clinical Characteristics of 185 Japanese Children With 46,XY Differences of Sex Development.
The Journal of clinical endocrinology and metabolismExperiences and psychological issues affecting parents of children born with atypical genitalia in India.
Journal of pediatric endocrinology & metabolism : JPEMGly183Ser homozygous mutation of the steroid 5-a reductase type 2 (SRD5A2) gene in a Brazilian patient: case report.
Journal of pediatric endocrinology & metabolism : JPEMNR5A1/SF-1 Collaborates with Inhibin α and the Androgen Receptor.
International journal of molecular sciencesApplication and insights of targeted next-generation sequencing in a large cohort of 46,XY disorders of sex development in Chinese.
Biology of sex differencesEvidence for NR2F2/COUP-TFII involvement in human testis development.
Scientific reportsGenomic technologies and the diagnosis of 46, XY differences of sex development.
AndrologyCharacteristic external genitalia in male neonates with 5α-reductase deficiency.
Endocrine journalRecommendations for 46,XY Disorders/Differences of Sex Development Across Two Decades: Insights from North American Pediatric Endocrinologists and Urologists.
Archives of sexual behaviorWorldwide cohort study of 46, XY differences/disorders of sex development genetic diagnoses: geographic and ethnic differences in variants.
Frontiers in geneticsDetection of Molecular Variations at Androgen Receptor Gene in 46,XY Differences in Sex Development Cases.
Indian journal of endocrinology and metabolismEndometriosis in a Prepubertal Patient with 46,XY Difference in Sex Development: A Case Report.
Journal of pediatric and adolescent gynecologyLong-term outcome of gender assignment in individuals with 46, XY DSD assigned female sex in multicultural society.
Journal of pediatric urologyClinical characteristics and surgical treatment of children with 45, X/46, XY differences of sex development.
Journal of pediatric urologyMutations in STARD8 (DLC3) May Cause 46,XY Gonadal Dysgenesis.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation[Value of the human chorionic gonadotropin stimulation test in the diagnosis of disorder of sexual development in children].
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatricsA Risk of Gonadoblastoma in Familial Swyer Syndrome-A Case Report and Literature Review.
Journal of clinical medicineNR5A1-related 46,XY partial gonadal dysgenesis: A case report and literature review.
MedicineDHX37 and the Implications in Disorders of Sex Development: An Update Review.
Hormone research in paediatricsLong-read genome sequencing reveals a novel intronic retroelement insertion in NR5A1 associated with 46,XY differences of sexual development.
American journal of medical genetics. Part APersistent Müllerian Duct Syndrome Diagnosed Incidentally: A Case Report.
JPMA. The Journal of the Pakistan Medical AssociationIn vitro functional study of fifteen SRD5A2 variants found in Chinese patients and the relation between the SRD5A2 genotypes and phenotypes.
The Journal of steroid biochemistry and molecular biologyDMRT1 is a testis-determining gene in rabbits and is also essential for female fertility.
eLifeMini review: Breast cancer care in individuals with differences of sexual development.
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical OncologyIntersex manifestation in the rainbow darter (Etheostoma caeruleum): Are adult male fish susceptible to developing and recovering from intersex after exposure to endocrine active compounds?
Aquatic toxicology (Amsterdam, Netherlands)A novel mutation in the AMHR2 gene, resulting in persistent Müllerian duct syndrome presenting with bilateral cryptorchidism and obstructed inguinal hernia.
Journal of pediatric endocrinology & metabolism : JPEMInduced pluripotent stem cell line generated from a patient with differences in sex development (DSD) and multiple genetic variants including a large deletion in NR5A1.
Stem cell researchDisorders of Sex Development in Office Practice.
Indian journal of pediatricsGenotype-phenotype correlations, surgical selections, and postoperative complications of 5α-reductase 2 deficiency in 69 children with hypospadias.
Asian journal of andrologyNuclear Receptor Gene Variants Underlying Disorders/Differences of Sex Development through Abnormal Testicular Development.
Biomolecules"Exogenous" 5 Alpha Reductase Deficiency: A Case Report.
UrologyThe genetic spectrum of a Chinese series of patients with 46, XY disorders of the sex development.
AndrologyA novel DEAH-box helicase 37 mutation associated with differences of sex development.
Frontiers in endocrinologyGenetic control of typical and atypical sex development.
Nature reviews. UrologyNew molecular insights into the A218V variant impact on the steroidogenic acute regulatory protein (STAR) associated with 46, XY disorders of sexual development.
Molecular genetics and genomics : MGGSexuality and fertility desire in a large cohort of individuals with 46, XY differences in sex development.
Clinics (Sao Paulo, Brazil)Genetic Variants in SRD5A2 in a Spectrum of DSD Patients from Australian Clinics Highlight Importance of Genetic Testing alongside Typical First-Line Investigations.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationPersistence of foetal testicular features in patients with defective androgen signalling.
European journal of endocrinologyAdditional evidence for the role of chromosomal imbalances and SOX8, ZNRF3 and HHAT gene variants in early human testis development.
Reproductive biology and endocrinology : RB&EModulatory activity of testosterone on growth pattern and IGF-1 levels in vanishing testis syndrome: a case report during 15 years of follow-up.
BMC endocrine disordersChanges in the clinical management of 5α-reductase type 2 and 17β-hydroxysteroid dehydrogenase type 3 deficiencies in France.
Endocrine connectionsChallenges in the Diagnosis of XY Differences of Sexual Development.
Medicina (Kaunas, Lithuania)Challenges Waiting for an Adult with DSD.
Hormone research in paediatricsDiagnostic approach in 46, XY DSD: an endocrine society of bengal (ESB) consensus statement.
Journal of pediatric endocrinology & metabolism : JPEMClinical characteristics of a male child with non-classic lipoid congenital adrenal hyperplasia and literature review.
Frontiers in endocrinologyElevated plasma miR-210 expression is associated with atypical genitalia in patients with 46,XY differences in sex development.
Molecular genetics & genomic medicineFGF9 variant in 46,XY DSD patient suggests a role for dimerization in sex determination.
Clinical geneticsAn Asian case of combined 17α-hydroxylase/17,20-lyase deficiency due to homozygous p.R96Q mutation: A case report and review of the literature.
Frontiers in endocrinologyA conserved function of Human DLC3 and Drosophila Cv-c in testis development.
eLifeNovel variant in HHAT as a cause of different sex development with partial gonadal dysgenesis associated with microcephaly, eye defects, and distal phalangeal hypoplasia of both thumbs: Case report.
Frontiers in endocrinologyLessons from 17β-HSD3 deficiency: Clinical spectrum and complex molecular basis in Chinese patients.
The Journal of steroid biochemistry and molecular biologyDisorder of Sex Development Due to 17-Beta-Hydroxysteroid Dehydrogenase Type 3 Deficiency: A Case Report and Review of 70 Different HSD17B3 Mutations Reported in 239 Patients.
International journal of molecular sciencesAnomalies in Human Sex Determination: Usefulness of a Combined Cytogenetic Approach to Characterize an Additional Case with Xp Functional Disomy Associated with 46,XY Gonadal Dysgenesis.
Journal of clinical research in pediatric endocrinologyTenuous Transcriptional Threshold of Human Sex Determination. I. SRY and Swyer Syndrome at the Edge of Ambiguity.
Frontiers in endocrinologyDHX37 and 46,XY DSD: A New Ribosomopathy?
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationCase Report: Novel Compound Heterozygotic Variants in PPP2R3C Gene Causing Syndromic 46, XY Gonadal Dysgenesis and Literature Review.
Frontiers in geneticsThe Molecular Basis of 5α-Reductase Type 2 Deficiency.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationCan Non-Coding NR5A1 Gene Variants Explain Phenotypes of Disorders of Sex Development?
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationA case of 46,XY disorders of sex development with congenital heart disease caused by a GATA4 variant.
Congenital anomaliesNon-obvious diagnosis and breast development in pure gonadal dysgenesis.
Ginekologia polskaClinical, Hormonal, and Genetic Characteristics of 5α-Reductase Type 2 Deficiency in 103 Chinese Patients.
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists46, XY Disorders of Sexual Development: a case report and theoretical framework.
Acta bio-medica : Atenei ParmensisCell adhesion and immune response, two main functions altered in the transcriptome of seasonally regressed testes of two mammalian species.
Journal of experimental zoology. Part B, Molecular and developmental evolutionDisorders of Sex Development in a Large Ukrainian Cohort: Clinical Diversity and Genetic Findings.
Frontiers in endocrinologyA rare cause of primary amenorrhea: LHCGR gene mutations.
European journal of obstetrics, gynecology, and reproductive biologyEffectiveness of dihydrotestosterone ointment on glans penis size increment in a 5-alpha-reductase type 2 deficiency patient.
Pediatrics international : official journal of the Japan Pediatric SocietyFertility in Individuals with Differences in Sex Development: Provider Knowledge Assessment.
Journal of pediatric and adolescent gynecologyGenetics of 46,XY gonadal dysgenesis.
Best practice & research. Clinical endocrinology & metabolismGenetics of anti-Müllerian hormone and its signaling pathway.
Best practice & research. Clinical endocrinology & metabolism17β hydroxysteroid dehydrogenase 3 deficiency in 46,XY disorders of sex development: Our experience and a gender role-focused systematic review.
Clinical endocrinologyContribution of Clinical and Genetic Approaches for Diagnosing 209 Index Cases With 46,XY Differences of Sex Development.
The Journal of clinical endocrinology and metabolismUnraveling a case of 46,XY DSD due to 17ß-Hydroxysteroid Dehydrogenase type 3 mutations at the age of 49.
Annales d'endocrinologieSexual Function in Women With Differences of Sex Development or Premature Loss of Gonadal Function.
The journal of sexual medicineSurgical management and molecular diagnosis of persistent Müllerian duct syndrome in Chinese patients.
Asian journal of andrologyChronic social defeat stress causes retinal vascular dysfunction.
Experimental eye researchDifferences of adrenal-derived androgens in 5α-reductase deficiency versus androgen insensitivity syndrome.
Clinical and translational scienceExpanding the spectrum of syndromic PPP2R3C-related XY gonadal dysgenesis to XX gonadal dysgenesis.
Clinical geneticsClinical, Biochemical, and Molecular Characterization of Indian Children with Clinically Suspected Androgen Insensitivity Syndrome.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationOne hundred twelve cases of 46, XY DSD patients after initial gender assignment: a short-term survey of gender role and gender dysphoria.
Orphanet journal of rare diseasesPubertal development in 46,XY patients with NR5A1 mutations.
EndocrineClinical Utility of Anti-Mullerian Hormone in Pediatrics.
The Journal of clinical endocrinology and metabolismOligogenic Causes of Human Differences of Sex Development: Facing the Challenge of Genetic Complexity.
Hormone research in paediatricsVariants in 46,XY DSD-Related Genes in Syndromic and Non-Syndromic Small for Gestational Age Children with Hypospadias.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationThe Desert Hedgehog Signalling Pathway in Human Gonadal Development and Differences of Sex Development.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationA Small Supernumerary Xp Marker Chromosome Including Genes NR0B1 and MAGEB Causing Partial Gonadal Dysgenesis and Gonadoblastoma.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationClinical, Hormonal, Genetic, and Molecular Characteristics in Androgen Insensitivity Syndrome in an Asian Indian Cohort from a Single Centre in Western India.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationThe laboratory in the multidisciplinary diagnosis of differences or disorders of sex development (DSD): III) Biochemical and genetic markers in the 46,XYIV) Proposals for the differential diagnosis of DSD.
Advances in laboratory medicineCharacteristics and possible mechanisms of 46, XY differences in sex development caused by novel compound variants in NR5A1 and MAP3K1.
Orphanet journal of rare diseasesA case of late diagnosis and management of 46 XY complete gonadal dysgenesis in adulthood.
Ginekologia polskaWhole exome sequencing and functional characterization increase diagnostic yield in siblings with a 46, XY difference of sexual development (DSD).
The Journal of steroid biochemistry and molecular biologyAdvances in genomic diagnosis of a large cohort of Egyptian patients with disorders of sex development.
American journal of medical genetics. Part AProphylactic gonadectomy in 46 XY females; why, where and when?
Hormone molecular biology and clinical investigationClinical phenotype and management of individuals with mosaic monosomy X with Y chromosome material stratified by genital phenotype.
American journal of medical genetics. Part AA case report of 46,XY partial gonadal dysgenesis caused by a novel mutation in the sex-determining region gene.
Translational pediatricsANDROGEN INSENSITIVITY SYNDROME,REVIEW OF LITERATURE BASED ON CASE REPORTS.
Georgian medical newsGender identity disorder (GID) in adolescents and adults with differences of sex development (DSD): A systematic review and meta-analysis.
Journal of pediatric urologyVariants of STAR, AMH and ZFPM2/FOG2 May Contribute towards the Broad Phenotype Observed in 46,XY DSD Patients with Heterozygous Variants of NR5A1.
International journal of molecular sciencesXY Gonadal Dysgenesis in a Phenotypic Female Identified by Direct-to-Consumer Genetic Testing.
PediatricsIdentification of four novel variant in the AMHR2 gene in six unrelated Turkish families.
Journal of endocrinological investigationDemetylation of the sex-determining region Y gene promoter and incidence of disorder of sex development in cloned dog males.
Journal of physiology and pharmacology : an official journal of the Polish Physiological SocietyPrevalence of gene mutations in a Chinese 46,XY disorders of sex development cohort detected by targeted next-generation sequencing.
Asian journal of andrology46,XY DSD and limb abnormalities in a female with a de novo LHX9 missense mutation.
American journal of medical genetics. Part AMolecular genetics of disorders of sex development in a highly consanguineous population.
The Journal of steroid biochemistry and molecular biologyMolecular genetic analysis of AKR1C2-4 and HSD17B6 genes in subjects 46,XY with hypospadias.
Journal of pediatric urologyA non-surgical approach to 46,XY differences in sex development through hormonal suppression at puberty: a single-center case series study.
EndocrineGenetic Analysis of 25 Patients with 5α-Reductase Deficiency in Chinese Population.
BioMed research internationalMonochorionic diamniotic twins of discordant external genitalia with 45,X/46,XY mosaicism.
Molecular genetics & genomic medicineA Case of 45,X/46,XY Mosaicism Presenting as Swyer Syndrome.
Journal of pediatric and adolescent gynecologyNR5A1 Gene Variants: Variable Phenotypes, New Variants, Different Outcomes.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationClinical, hormonal and genetic characteristics of androgen insensitivity syndrome in 39 Chinese patients.
Reproductive biology and endocrinology : RB&EMutational Analysis of the Putative Anti-Müllerian Hormone (AMH) Binding Interface on its Type II Receptor, AMHR2.
EndocrinologyPersistent Müllerian duct syndrome: an update.
Reproduction, fertility, and developmentOligogenic Origin of Differences of Sex Development in Humans.
International journal of molecular sciencesHigh Molecular Diagnosis Rate in Undermasculinized Males with Differences in Sex Development Using a Stepwise Approach.
EndocrinologyAnalysis of variants in GATA4 and FOG2/ZFPM2 demonstrates benign contribution to 46,XY disorders of sex development.
Molecular genetics & genomic medicineA rare cause of delayed puberty in two cases with 46,XX and 46,XY karyotype: 17 α-hydroxylase deficiency due to a novel variant in CYP17A1 gene.
Gynecological endocrinology : the official journal of the International Society of Gynecological EndocrinologyClinical Findings and Follow-Up of 46,XY and 45,X/46,XY Testicular Dysgenesis.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationThe XY Female: Exploring Care for Adolescent Girls with Complete Androgen Insensitivity Syndrome.
Comprehensive child and adolescent nursingDisorders Of Sex Differentiation: Evaluation And Management, A Dilemma.
Journal of Ayub Medical College, Abbottabad : JAMCMutation update for the NR5A1 gene involved in DSD and infertility.
Human mutationSex Assignment and Diagnostics in Infants with Ambiguous Genitalia - A Single-Center Retrospective Study.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationManagement of 46,XY Differences/Disorders of Sex Development (DSD) Throughout Life.
Endocrine reviewsThe importance of the multiplex ligation-dependent probe amplification in the identification of a novel two-exon deletion of the NR5A1 gene in a patient with 46,XY differences of sex development.
Molecular biology reportsPathogenic variants in the DEAH-box RNA helicase DHX37 are a frequent cause of 46,XY gonadal dysgenesis and 46,XY testicular regression syndrome.
Genetics in medicine : official journal of the American College of Medical GeneticsGenetic Evidence of the Association of DEAH-Box Helicase 37 Defects With 46,XY Gonadal Dysgenesis Spectrum.
The Journal of clinical endocrinology and metabolismA mutation inactivating the distal SF1 binding site on the human anti-Müllerian hormone promoter causes persistent Müllerian duct syndrome.
Human molecular genetics[Gender selection and postoperative follow-up analysis in 85 children with 46, XY disorders of sex development].
Zhonghua er ke za zhi = Chinese journal of pediatricsSerum steroid profiling in Cushing's syndrome patients.
The Journal of steroid biochemistry and molecular biologyNew insights into 5α-reductase type 2 deficiency based on a multi-centre study: regional distribution and genotype-phenotype profiling of SRD5A2 in 190 Chinese patients.
Journal of medical geneticsCompound heterozygous mutations in the luteinizing hormone receptor signal peptide causing 46,XY disorder of sex development.
European journal of endocrinologyVoice dissatisfaction in individuals with a disorder of sex development.
Clinical endocrinologyFunctional analysis of novel desert hedgehog gene variants improves the clinical interpretation of genomic data and provides a more accurate diagnosis for patients with 46,XY differences of sex development.
Journal of medical geneticsTESTICULAR REGRESSION SYNDROME: PRACTICE VARIATION IN DIAGNOSIS AND MANAGEMENT.
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical EndocrinologistsEstablishing reproductive potential and advances in fertility preservation techniques for XY individuals with differences in sex development.
Clinical endocrinologyPPP2R3C gene variants cause syndromic 46,XY gonadal dysgenesis and impaired spermatogenesis in humans.
European journal of endocrinology[Clinical phenotype and gene analysis of 86 cases of 5 alpha reductase deficiency].
Zhonghua er ke za zhi = Chinese journal of pediatricsTri-allelic expression of HLA gene in 46,XX/46,XY chimerism.
Transplant immunologyHuman sex reversal is caused by duplication or deletion of core enhancers upstream of SOX9.
Nature communicationsIntegrating clinical and genetic approaches in the diagnosis of 46,XY disorders of sex development.
Endocrine connectionsPersistent Mullerian duct syndrome: Report of two cases with phenotypical immunohistochemical profiling.
Urologia[Differences of Sex Development (DSD): Controversies and Challenges].
Annales d'endocrinologieSertoli Cell Tumour and Uterine Leiomyoma in Miniature Schnauzer Dogs with Persistent Müllerian Duct Syndrome Caused by Mutation in the AMHR2 Gene.
Journal of comparative pathologyChildhood Sex-Typed Behavior and Gender Change in Individuals with 46,XY and 46,XX Disorders of Sex Development: An Iranian Multicenter Study.
Archives of sexual behaviorNovel homozygous nonsense mutations in LHCGR lead to empty follicle syndrome and 46, XY disorder of sex development.
Human reproduction (Oxford, England)A Novel Mutation of AMHR2 in Two Siblings with Persistent Müllerian Duct Syndrome.
Journal of clinical research in pediatric endocrinologyClinical aspects of 49 infertile males with 45,X/46,XY mosaicism karyotype: A case series.
AndrologiaPrenatal testosterone and theory of mind development: Findings from disorders of sex development.
PsychoneuroendocrinologyPhenotypic Variation in 46,XX Disorders of Sex Development due to the NR5A1 p.R92W Variant: A Sibling Case Report and Literature Review.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationIdentification of novel candidate genes for 46,XY disorders of sex development (DSD) using a C57BL/6J-Y POS mouse model.
Biology of sex differencesMutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies.
Human molecular geneticsGrowth, sexual and bone development in a boy with bilateral anorchia under testosterone treatment guided by the development of his monozygotic twin.
Journal of pediatric endocrinology & metabolism : JPEMRecurrent Intragenic Duplication within the NR5A1 Gene and Severe Proximal Hypospadias.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationPartial androgen insensitivity syndrome due to somatic mosaicism of the androgen receptor.
Journal of pediatric endocrinology & metabolism : JPEMA Novel Sex Chromosome Mosaicism 45,X/45,Y/46,XY/46,YY/47,XYY Causing Ambiguous Genitalia.
Annals of clinical and laboratory scienceBiallelic and monoallelic ESR2 variants associated with 46,XY disorders of sex development.
Genetics in medicine : official journal of the American College of Medical GeneticsFunctional Impact of Novel Androgen Receptor Mutations on the Clinical Manifestation of Androgen Insensitivity Syndrome.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationFour Novel NR5A1 Mutations in 46,XY Gonadal Dysgenesis Patients Including Frameshift Mutations with Altered Subcellular SF-1 Localization.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationRisk association of congenital anomalies in patients with ambiguous genitalia: A 22-year single-center experience.
Journal of pediatric urologyHuman Chorionic Gonadotropin Test: Old Uncertainties, New Perspectives, and Value in 46,XY Disorders of Sex Development.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationBiallelic mutations in FLNB cause a skeletal dysplasia with 46,XY gonadal dysgenesis by activating β-catenin.
Clinical geneticsMultiparameter Investigation of a 46,XX/46,XY Tetragametic Chimeric Phenotypical Male Patient with Bilateral Scrotal Ovotestes and Ovulatory Activity.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation17β-Hydroxysteroid dehydrogenase 3 deficiency: Three case reports and a systematic review.
The Journal of steroid biochemistry and molecular biologyHeterogeneity of human WT1 gene.
Postepy higieny i medycyny doswiadczalnej (Online)The possible role of AMH in shortening the gubernacular cord in testicular descent: A reappraisal of the evidence.
Journal of pediatric surgeryThe Persistent Müllerian Duct Syndrome: An Update Based Upon a Personal Experience of 157 Cases.
Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiationClinical heterogeneity in children with gonadal dysgenesis associated with non-mosaic 46,XY karyotype.
Journal of pediatric urologyBirth Weight in Different Etiologies of Disorders of Sex Development.
The Journal of clinical endocrinology and metabolism17α-HYDROXYLASE/17, 20-LYASE DEFICIENCY: CLINICAL AND MOLECULAR CHARACTERIZATION OF EIGHT CHINESE PATIENTS.
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical EndocrinologistsAssociações
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Identification of Novel and Known Variants in Epigenetic Genes Associated with Syndromic 46,XY Differences of Sex Development among Moroccan Patients.Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation· 2026· PMID 41666144mais citado
- Rare phenotypic spectrum of 17β-hydroxysteroid dehydrogenase 3 deficiency: case series from infancy to adolescence.
- Upstream SOX9 deletion in a 46,XY girl with acampomelic campomelic dysplasia and absent minipuberty.
- Molecular genetic diagnosis and surgical management in a cohort of children with 46,XY disorders/differences of sex development.
- Functional analysis of SRY variants in individuals with 46,XY differences of sex development.
- Close relationship, similar phenotype of GATA4 and NR5A1 mutations: gonadal dysgenesis and puberty development.
- Pubertal Development as a Marker of Gonadal Neoplasm in 46XY Complete Gonadal Dysgenesis.
- Phenotypic Variation and Pubertal Outcomes in Males and Females With 46,XY Partial Gonadal Dysgenesis.
- [Value of the human chorionic gonadotropin stimulation test in the diagnosis of disorder of sexual development in children].
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:98085(Orphanet)
- MONDO:0020040(MONDO)
- GARD:8538(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Artigo Wikipedia(Wikipedia)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
