Doença caracterizada por perda auditiva que não faz parte de uma síndrome maior.
Introdução
O que você precisa saber de cara
A **surdez genética não sindrômica** é uma alteração congênita ou infantil que provoca perda auditiva neurossensorial grave sem fazer parte de uma síndrome clínica maior. Ela ocorre por mutações em genes como AIFM1, TMC1 e TECTA, podendo ter diferentes tipos de herança familiar. O sinal principal observado pela família é a dificuldade de audição desde os primeiros anos de vida. Esta condição não consta na lista oficial de PCDT de doenças raras do Ministério da Saúde, sendo acompanhada pela rede geral de saúde auditiva do SUS.
Doença caracterizada por perda auditiva que não faz parte de uma síndrome maior.
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
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Entender a doença
Do básico ao detalhe, leia no seu ritmo
Preparando trilha educativa...
Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 26 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 94 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
75 genes identificados com associação a esta condição. Padrão de herança: Autosomal dominant, Autosomal recessive, X-linked recessive.
Curadoria gene-doença
fontes oficiaisCombined oxidative phosphorylation deficiency 6
A mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting. Some patients manifest prenatal ventriculomegaly and severe postnatal encephalomyopathy.
Deafness, autosomal recessive, 108
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal recessive, 15
A form of non-syndromic sensorineural hearing loss with prelingual onset. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal dominant, 36
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA36 is a bilateral hearing loss, and begins at 5-10 years of age. It progresses to profound deafness within 10-15 years.
Polyendocrine-polyneuropathy syndrome
A progressive endocrine and neurodevelopmental disorder manifesting early in childhood with growth retardation and recurrent episodes of profound asymptomatic hypoglycemia. PEPNS is characterized by central hypothyroidism, hypogonadotropic hypogonadism, incomplete puberty, progressive non-autoimmune insulin-dependent diabetes mellitus, peripheral demyelinating sensorimotor polyneuropathy, and cerebellar and pyramidal signs.
Combined oxidative phosphorylation deficiency 13
A mitochondrial disorder characterized by early onset severe encephalomyopathy, dystonia, choreoathetosis, bucofacial dyskinesias and combined mitochondrial respiratory chain deficiency. Nerve conductions velocities are decreased. Levels of plasma and cerebrospinal fluid lactate are increased.
Dyslexia 2
A relatively common, complex cognitive disorder characterized by an impairment of reading performance despite adequate motivational, educational and intellectual opportunities. It is a multifactorial trait, with evidence for familial clustering and heritability.
Deafness, autosomal dominant, 12
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal recessive, 112
A form of non-syndromic, sensorineural deafness characterized by postlingual progressive hearing impairment. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal dominant, 44
A form of non-syndromic deafness characterized by initially moderate hearing loss that affects mainly low to mid frequencies. Later, it progresses to involve all the frequencies and leads to a profound hearing loss by the 6th decade.
Periventricular nodular heterotopia 9
A form of periventricular nodular heterotopia, a disorder resulting from a defect in the pattern of neuronal migration in which ectopic collections of neurons lie along the lateral ventricles of the brain or just beneath, contiguously or in isolated patches. PVNH9 is an autosomal dominant disorder with incomplete penetrance, characterized by impaired intellectual development, cognitive defects, learning disabilities, and behavior abnormalities. Some patients develop seizures.
Deafness, autosomal dominant, 66
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal recessive, 84B
A form of non-syndromic deafness characterized by congenital, non-progressive, sensorineural, symmetric hearing loss. Vestibular hypofunction is rarely observed.
Deafness, autosomal recessive, 76
A form of non-syndromic sensorineural deafness, a disorder resulting from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB76 affected individuals have onset of progressive high frequency hearing impairment between birth and 6 years of age. The hearing loss is severe at high frequencies by adulthood.
Deafness, autosomal recessive, 31
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal dominant, 74
A form of non-syndromic deafness characterized by progressive, postlingual hearing loss with onset in the third decade of life.
Diarrhea 15, congenital
An autosomal recessive disorder characterized by severe diarrhea manifesting in infancy and resolving by the second year of life.
Deafness, autosomal recessive, 49
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Chudley-McCullough syndrome
An autosomal recessive neurologic disorder characterized by early-onset sensorineural deafness and specific brain anomalies on MRI, including hypoplasia of the corpus callosum, enlarged cysterna magna with mild focal cerebellar dysplasia, and nodular heterotopia. Some patients have hydrocephalus. Psychomotor development is normal.
Deafness, autosomal recessive, 119
A form of non-syndromic deafness characterized by mild to profound sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal recessive, 59
A form of sensorineural hearing impairment with absent or severely abnormal auditory brainstem response but normal otoacoustic emissions (auditory neuropathy or auditory dys-synchrony). Auditory neuropathies result from a lesion in the area including the inner hair cells, connections between the inner hair cells and the cochlear branch of the auditory nerve, the auditory nerve itself and auditory pathways of the brainstem.
Erythrokeratodermia variabilis et progressiva 1
A form of erythrokeratodermia variabilis et progressiva, a genodermatosis characterized by the coexistence of two independent skin lesions: transient erythema and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases.
Wolfram syndrome 1
A rare disorder characterized by juvenile-onset insulin-dependent diabetes mellitus with optic atrophy. Other manifestations include diabetes insipidus, sensorineural deafness, dementia, psychiatric illnesses.
Deafness, autosomal dominant, 40
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Auditory neuropathy, autosomal dominant 1
A form of sensorineural hearing loss with absent or severely abnormal auditory brainstem response, in the presence of normal cochlear outer hair cell function and normal otoacoustic emissions. Auditory neuropathies result from a lesion in the area including the inner hair cells, connections between the inner hair cells and the cochlear branch of the auditory nerve, the auditory nerve itself and auditory pathways of the brainstem. Affected individuals typically respond to sound but have difficulties in speech discrimination.
Wilms tumor 6
A pediatric malignancy of kidney, and the most common childhood abdominal malignancy. It is caused by the uncontrolled multiplication of renal stem, stromal, and epithelial cells.
Deafness, autosomal dominant, 15
A form of non-syndromic hearing loss with variable phenotype in terms of age at onset, levels of progression, and shape of audiograms.
Otospondylomegaepiphyseal dysplasia, autosomal dominant
An autosomal dominant form of otospondylomegaepiphyseal dysplasia, a disorder characterized by sensorineural deafness, enlarged epiphyses, mild platyspondyly, and disproportionate shortness of the limbs. Total body length is normal. Typical facial features are mid-face hypoplasia, short upturned nose and depressed nasal bridge. Most patients have Pierre Robin sequence including an opening in the roof of the mouth (cleft palate) and a small lower jaw (micrognathia). Ocular symptoms are absent. Some patients have early-onset osteoarthritis.
Deafness, autosomal recessive, 106
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal recessive, 8
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal recessive, 68
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal recessive, 29
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Usher syndrome 1F
USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness.
Deafness, autosomal recessive, 117
A form of non-syndromic deafness characterized by prelingual, moderate-to-profound sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal recessive, 30
A form of non-syndromic deafness characterized by bilateral progressive hearing loss, which first affects the high frequencies. Hearing loss begins in the second decade, and by age 50 is severe in high and middle frequencies and moderate at low frequencies.
Familial infantile myoclonic epilepsy
A subtype of idiopathic epilepsy starting in early infancy and manifesting as myoclonic seizures, febrile convulsions, and tonic-clonic seizures.
Deafness, autosomal recessive, 104
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, X-linked, 2
A form of deafness characterized by both conductive hearing loss resulting from stapes (perilymphatic gusher) fixation, and progressive sensorineural deafness.
Seizures, sensorineural deafness, ataxia, impaired intellectual development, and electrolyte imbalance
A complex disorder characterized by generalized seizures with onset in infancy, delayed psychomotor development, ataxia, sensorineural hearing loss, hypokalemia, metabolic alkalosis, and hypomagnesemia.
Deafness, autosomal recessive, 84A
A form of non-syndromic deafness characterized by progressive, sensorineural hearing loss and vestibular dysfunction.
Deafness, autosomal recessive, 6
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal recessive, 35
A form of non-syndromic deafness characterized by non-progressive, prelingual hearing loss.
Deafness, autosomal recessive, 28
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal recessive, 22
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Usher syndrome 1C
USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness.
Deafness, autosomal dominant, 4B
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal dominant, 10
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal recessive, 93
A form of non-syndromic deafness characterized by stable, bilateral, symmetric, prelingual moderate to severe deafness. Hearing impairment is slightly more pronounced in the mid-frequencies, resulting in a distinctive shallow U-shaped audiogram.
Deafness, autosomal recessive, 9
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal recessive, 79
A form of non-syndromic deafness characterized by progressive and severe sensorineural hearing loss. There are no symptoms of vestibular dysfunction.
Pendred syndrome
An autosomal recessive disorder characterized by congenital sensorineural hearing loss in association with thyroid goiter. The disorder may account for up to 10% of the cases of hereditary deafness. The deafness is most often associated with a Mondini cochlear defect. Deafness occurs early, starting at birth or during the first years of life. It is bilateral, sometimes asymmetrical, fluctuant and often progressive. Thyroid perturbations, such as thyroid goiter and/or hypothyroidism appear most commonly during adolescence, but they can be congenital or appear later.
Deafness, autosomal recessive, 16
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal recessive, 124
A form of non-syndromic deafness characterized by progressive sensorineural hearing loss with onset at birth. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal recessive, 120
A form of non-syndromic deafness characterized by congenital or prelingual onset of severe to profound sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Usher syndrome 1D
USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness.
Deafness, autosomal dominant, 85
A form of non-syndromic, sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA85 is characterized by progressive hearing loss, with onset in childhood or young adulthood.
Deafness, autosomal dominant, 56
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA56 is characterized by progressive hearing impairment with postlingual onset.
Deafness, autosomal dominant, 4A
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Stickler syndrome 2
An autosomal dominant form of Stickler syndrome, an inherited disorder that associates ocular signs with more or less complete forms of Pierre Robin sequence, bone disorders and sensorineural deafness. Ocular disorders may include juvenile cataract, myopia, strabismus, vitreoretinal or chorioretinal degeneration, retinal detachment, and chronic uveitis. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a large tongue (macroglossia), and a small lower jaw (micrognathia). Bones are affected by slight platyspondylisis and large, often defective epiphyses. Juvenile joint laxity is followed by early signs of arthrosis. The degree of hearing loss varies among affected individuals and may become more severe over time. Syndrome expressivity is variable.
Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss
An autosomal dominant disorder characterized by thrombocytopenia, giant platelets and Dohle body-like inclusions in peripheral blood leukocytes with variable ultrastructural appearance. Some affected individuals lack leukocyte inclusion bodies on classic staining of peripheral blood smears. Alport syndrome-like features of nephritis, hearing loss, and eye abnormalities are present in some patients.
Usher syndrome 1B
USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness.
Deafness, autosomal recessive, 57
A form of non-syndromic, sensorineural deafness characterized by symmetric, bilateral hearing loss with onset in early childhood. Vestibular function is preserved. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB57 severity ranges from moderate to severe.
Ectodermal dysplasia 2, Clouston type
A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ECTD2 is an autosomal dominant condition characterized by atrichosis, nail hypoplasia and deformities, hyperpigmentation of the skin, normal teeth, normal sweat and sebaceous gland function. Palmoplantar hyperkeratosis is a frequent feature. Hearing impairment has been detected in few cases.
Deafness, autosomal recessive, 116
A form of non-syndromic deafness characterized by slowly progressive, moderate to profound sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal recessive, 100
A form of non-syndromic, sensorineural deafness characterized by prelingual hearing impairment. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Renal hypodysplasia/aplasia 3
A severe, autosomal dominant disease encompassing a spectrum of kidney development defects. Clinical manifestations are highly variable and include bilateral or unilateral renal agenesis, renal aplasia, hypoplasia, (cystic) dysplasia, severe obstructive uropathy, and vesicoureteral reflux. Bilateral renal agenesis is almost invariably fatal in utero or in the perinatal period. Unilateral renal agenesis can lead to future health issues including end-stage renal disease.
Deafness, autosomal dominant, 2A
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal dominant, 28
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA28 is characterized by mild to moderate hearing loss across most frequencies that progresses to severe loss in the higher frequencies by the fifth decade.
Variantes genéticas (ClinVar)
429 variantes patogênicas registradas no ClinVar.
Vias biológicas (Reactome)
86 vias biológicas associadas aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Surdez genética não sindrômica
Selecione um estado ou use sua localização para ver resultados.
Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Pesquisa e ensaios clínicos
Nenhum ensaio clínico registrado para esta condição.
Publicações mais relevantes
Late diagnosis of Heimler syndrome and review of the genetic and phenotypic spectrum.
Heimler syndrome is a rare autosomal recessive disorder at the mild end of the peroxisomal biogenesis disorders (PBDs), characterized by sensorineural hearing loss, amelogenesis imperfecta, and retinal dystrophy. Nail abnormalities affect a minority. We present a 67-year-old woman diagnosed with non-syndromic retinitis pigmentosa in her fifties, who was later found to carry compound heterozygous variants in the PEX6 gene. Her medical history included prelingual hearing loss, early tooth decay, and brittle nails that were deemed unrelated for decades. Hearing loss and vision loss remained relatively stable up to last consultation. Our literature review includes 46 published Heimler syndrome cases with confirmed molecular diagnoses. Retinal dystrophy, predominantly of the rod-cone type with pigment clumping, was present in 89% of reported cases, with macular edema noted in 40%. Serum peroxisomal metabolite abnormalities seem to correlate with worse neurodevelopmental outcomes. There are no clear genotype-phenotype correlations, although residual peroxisomal function due to the presence of at least one missense, leaky splice site, or stable truncated allele explains the relatively mild phenotype for PBD. We underscore the importance to include syndromic disorders in the differential diagnosis of retinal dystrophy in older adults.
Whole exome sequencing reveals novel and rare variants in nonsyndromic hearing loss-related genes: A focus on GPSM2 compound heterozygosity.
Non-syndromic hearing loss (NSHL) is a genetically heterogeneous disorder affecting millions worldwide. Recent advances in genetic technologies have expanded our understanding of its molecular basis, but challenges remain in identifying and interpreting causative variants. This study aimed to investigate the genetic etiology of NSHL using comprehensive genetic screening, with a focus on identifying rare and potentially pathogenic variants. We performed genetic analysis on 43 participants diagnosed with NSHL using whole exome sequencing (WES) technology. Variant filtering, in silico prediction tools, and segregation analysis were employed to evaluate the pathogenicity of identified variants. Our analysis revealed 20 rare and deleterious variants (4 novel and 16 previously reported) in 16 NSHL-related genes among 43 participants. These variants included 3 known pathogenic, 4 likely pathogenic, and 13 variants of uncertain significance (VUS). Notably, we identified compound heterozygous variants in the GPSM2 gene (NM_013296:c.185G>A;p.Ser62Asn and NM_013296:c.1264delG;p.Val422Tyrfs*28) in one participant, with segregation analysis confirming their trans configuration. This study expands our understanding of the genetic landscape of NSHL by identifying several rare variants in known NSHL-related genes. Notably, we report the first case of compound heterozygous variants in the GPSM2 gene in the Indian population, a finding not previously documented. This discovery underscores the importance of comprehensive genetic screening in diverse populations and contributes to the growing body of evidence for the role of GPSM2 in NSHL.
Mendelian non-syndromic and syndromic hearing loss genes contribute to presbycusis.
Age-related (AR) hearing loss (HL) is the most prevalent sensorineural disorder in older adults. Here we demonstrate that rare-variants in well-established Mendelian HL genes play an important role in ARHL etiology. In all we identified 32 Mendelian HL genes which are associated with ARHL. We performed single and rare-variant aggregate association analyses using exome data obtained from white-Europeans with self-reported hearing phenotypes from the UK Biobank. Our analysis revealed previously unreported associations between ARHL and rare-variants in Mendelian non-syndromic and syndromic HL genes, including MYO15A, and WFS1. Additionally, rare-variant aggregate association analyses identified associations with Mendelian HL genes i.e., ACTG1, GRHL2, KCNQ4, MYO7A, PLS1, TMPRSS3, and TNRC6B. Four novel ARHL genes were also detected: FBXO2 and PALM3, implicated in HL in mice, TWF1, associated with HL in Dalmatian dogs, and TXNDC17. In-silico analyses provided further evidence of inner ear expression of these genes in both murine and human models, supporting their relevance to ARHL. Analysis of variants with minor allele frequency >0.005 revealed additional ARHL associations with known e.g., ILDR1 and novel i.e., ABHD12, COA8, KANSL1, SERAC1, and UBE3B Mendelian non-syndromic and syndromic HL genes as well as ARHL associations with genes that have not been previously reported to be involved in HL e.g., VCL. Rare-variants in Mendelian HL genes typically exhibited higher effect sizes for ARHL compared to those in other associated genes. In conclusion, this study highlights the critical role Mendelian non-syndromic and syndromic HL genes play in the etiology of ARHL.
Leveraging underrepresented population data improves interpretation of genetic variants associated with hearing loss.
Hearing loss is genetically heterogeneous, with over 121 implicated genes. Minor allele frequency (MAF) data from population databases greatly aid variant interpretation; however, these databases are predominantly based on individuals of European ancestry and lack sufficient East Asian representation, limiting accurate interpretation in under-represented populations. We analyzed rare variants associated with non-syndromic hearing loss classified as pathogenic, likely pathogenic, or of uncertain significance in the Deafness Variation Database (DVD). Population allele frequencies from 9,579 Koreans, 54,000 Japanese, and 651 patients with sensorineural hearing loss were evaluated. Of the 6,381 pathogenic or likely pathogenic variants cataloged in the DVD, 216 (3.38%) were detected in Korean population. Among these, 31 variants exhibited high allele frequencies that exceeded thresholds typically applied to identify benign variants in clinical interpretation guidelines. Of these, 6 remained disease-causing, including 4 East Asian founder alleles and one MYO7A variant common in Koreans. Our pipeline identified 24 variants for reclassification as benign or likely benign, and one P2RX2 variant of uncertain significance. Of 1,299,211 VUS, 3,736 were reclassified as benign. A substantial number of variants previously classified as pathogenic were reclassified as benign using MAF data from under-represented populations, highlighting the need for large-scale sequencing in diverse ancestries.
The role of SLC19A2 variants in the wide spectrum of non-autoimmune abnormalities of glucose homeostasis.
Biallelic pathogenic variants in SLC19A2 (the solute carrier family 19 member 2, which encodes thiamine transporter 1, responsible for thiamine intake) cause a recessive syndromic diabetes of infancy or early childhood in the context of thiamine-responsive megaloblastic anaemia, characterised by sensorineural deafness. Indeed, it has been reported, although only once, that even a heterozygous missense loss-of-function variant of SLC19A2 causes dominantly inherited non-syndromic diabetes. Finally, it is unknown whether rare SLC19A2 pathogenic variants modulate the risk of type 2 diabetes at the population level. We investigated the role of SLC19A2 heterozygous variants in both autosomal dominant mild hyperglycaemia and type 2 diabetes. We performed whole exome sequencing in two probands with mild hyperglycaemia and in 191,140 samples from the UK Biobank. Here we report two different heterozygous missense likely pathogenic variants of SLC19A2 (NM_006996.2) associated with non-syndromic mild hyperglycaemia in two pedigrees (c.515G>T and c.1063A>C missense variants, respectively), clearly confirming the only report available so far suggesting this link. In both pedigrees, individuals who carried an additional variant in one of the established monogenic diabetes genes (i.e. PDX1, NM_000209.3 and KCNJ11, NM_000525.3) showed an anticipation of disease onset of 25-31 years. Finally, 12 rare null variants in SLC19A2 were associated with type 2 diabetes (p=0.00033; OR 3.7; 95% CI 1.3, 227) and increased HbA1c levels (p=0.019, effect [π]=2.2 ± 0.92) in the UK Biobank. Taken together with previous evidence, these data indicate that SLC19A2 variability modulates glucose homeostasis, from recessive syndromic diabetes, to autosomal dominant mild hyperglycaemia, to type 2 diabetes.
Publicações recentes
Late diagnosis of Heimler syndrome and review of the genetic and phenotypic spectrum.
Whole exome sequencing reveals novel and rare variants in nonsyndromic hearing loss-related genes: A focus on GPSM2 compound heterozygosity.
Oligogenic effect is associated with the clinical heterogeneity of autosomal dominant deafness-15.
The phenotypic spectrum of CEP250 gene variants.
Investigating Splice Defects in USH2A Using Targeted Long-Read Sequencing.
📚 EuropePMCmostrando 87
Late diagnosis of Heimler syndrome and review of the genetic and phenotypic spectrum.
Ophthalmic geneticsLeveraging underrepresented population data improves interpretation of genetic variants associated with hearing loss.
Scientific reportsThe role of SLC19A2 variants in the wide spectrum of non-autoimmune abnormalities of glucose homeostasis.
DiabetologiaWhole exome sequencing reveals novel and rare variants in nonsyndromic hearing loss-related genes: A focus on GPSM2 compound heterozygosity.
Journal of biosciences[Phenotypic and pathogenic variant analysis of an X-linked dominant inherited non-syndromic hearing loss pedigree].
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgeryMendelian non-syndromic and syndromic hearing loss genes contribute to presbycusis.
European journal of human genetics : EJHGOligogenic effect is associated with the clinical heterogeneity of autosomal dominant deafness-15.
Scientific reportsNext-Generation Sequencing of Chinese Children with Congenital Hearing Loss Reveals Rare and Novel Variants in Known and Candidate Genes.
BiomedicinesOverview of typical dental abnormalities in rare genetic syndromes occurring in the Czech Roma population.
Bratislavske lekarske listyThe phenotypic spectrum of CEP250 gene variants.
Ophthalmic geneticsA case with short stature and proteinuria: atypical presentation of a family with m.3243A>G mutation.
The Turkish journal of pediatricsRevising pathogenesis of AP1S1-related MEDNIK syndrome: a missense variant in the AP1S1 gene as a causal genetic lesion.
Journal of molecular medicine (Berlin, Germany)Investigating Splice Defects in USH2A Using Targeted Long-Read Sequencing.
CellsA Novel Variant in the DIAPH1 Gene Causing Macrothrombocytopenia and Non-syndromic Hearing Loss in a Pediatric Saudi Girl.
CureusHigh prevalence of exon-13 variants in USH2A-related retinal dystrophies in Taiwanese population.
Orphanet journal of rare diseasesMutation spectrum of hearing loss patients in Northwest China: Identification of 20 novel variants.
Molecular genetics & genomic medicineSelf-Reported Functional Vision in USH2A-Associated Retinal Degeneration as Measured by the Michigan Retinal Degeneration Questionnaire.
Investigative ophthalmology & visual scienceThe Segregation of p.Arg68Ter-CLDN14 Mutation in a Syrian Deaf Family, Phenotypic Variations, and Comparative Analysis with the GJB2 Gene.
GenesCurrent phenotypic and genetic spectrum of syndromic deafness in Tunisia: paving the way for precision auditory health.
Frontiers in geneticsInvestigation of a novel TBC1D24 variation causing autosomal dominant non-syndromic hearing loss.
Scientific reportsExpanding Genotype-Phenotype Correlation of CLCNKA and CLCNKB Variants Linked to Hearing Loss.
International journal of molecular sciencesNovel autosomal dominant TMC1 variants linked to hearing loss: insight into protein-lipid interactions.
BMC medical genomicsClinical relevance of the TECTA c.6183G>T variant identified in a family with autosomal dominant hearing loss: a case report.
Croatian medical journalCombined Presence in Heterozygosis of Two Variant Usher Syndrome Genes in Two Siblings Affected by Isolated Profound Age-Related Hearing Loss.
BiomedicinesFunctional Consequences of Pathogenic Variants of the GJB2 Gene (Cx26) Localized in Different Cx26 Domains.
BiomoleculesAutosomal dominant non-syndromic hearing loss caused by a novel mutation in MYO7A: A case report and review of the literature.
World journal of clinical casesClinical and genetic characteristics of a patient with phosphoribosyl pyrophosphate synthetase 1 deficiency and a systematic literature review.
Molecular genetics and metabolism reportsPhenotypic and molecular basis of SIX1 variants linked to non-syndromic deafness and atypical branchio-otic syndrome in South Korea.
Scientific reportsUSH2A mutational spectrum causing syndromic and non-syndromic retinal dystrophies in a large cohort of Mexican patients.
Molecular visionLoss-of-function mutations in MYO15A and OTOF cause non-syndromic hearing loss in two Yemeni families.
Human genomicsInsights into the pathophysiology of DFNA44 hearing loss associated with CCDC50 frameshift variants.
Disease models & mechanismsMonogenic Causes of Low-Frequency Non-Syndromic Hearing Loss.
Audiology & neuro-otologyRare Coding Variants in Patients with Non-Syndromic Vestibular Dysfunction.
GenesCalcium signaling and genetic rare diseases: An auditory perspective.
Cell calciumWhole genome sequencing for USH2A-associated disease reveals several pathogenic deep-intronic variants that are amenable to splice correction.
HGG advancesA novel frameshift variant of LMX1A that leads to autosomal dominant non-syndromic sensorineural hearing loss: functional characterization of the C-terminal domain in LMX1A.
Human molecular geneticsCase report: De novo pathogenic variant in WFS1 causes Wolfram-like syndrome debuting with congenital bilateral deafness.
Frontiers in geneticsInherited Retinal Dystrophy in Southeastern United States: Characterization of South Carolina Patients and Comparative Literature Review.
GenesRetinal Phenotype of Patients with CLRN1-Associated Usher 3A Syndrome in French Light4Deaf Cohort.
Investigative ophthalmology & visual scienceWhole exome analysis of patients in Japan with hearing loss reveals high heterogeneity among responsible and novel candidate genes.
Orphanet journal of rare diseasesGenetic profiles of non-syndromic severe-profound hearing loss in Chinese Hans by whole-exome sequencing.
GeneGenomic study of a large family with complex neurological phenotype including hearing loss, imbalance and action tremor.
Neurobiology of agingVariant analysis of 92 Chinese Han families with hearing loss.
BMC medical genomicsDe Novo ACTG1 Variant Expands the Phenotype and Genotype of Partial Deafness and Baraitser-Winter Syndrome.
International journal of molecular sciencesEvaluation of copy number variants for genetic hearing loss: a review of current approaches and recent findings.
Human geneticsPrevalence and phenotypic features of diabetes due to recessive, non-syndromic WFS1 mutations.
European journal of endocrinology[Genetic testing of a Chinese pedigree affected with non-syndromic autosomal dominant deafness 15].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsPrediction and interpretation of rare missense variant in OTOG associated with hearing loss.
GenomicsA New Pathogenic Variant in POU3F4 Causing Deafness Due to an Incomplete Partition of the Cochlea Paved the Way for Innovative Surgery.
GenesMolecular alteration in the Gap Junction Beta 2 (GJB2) gene associated with non-syndromic sensorineural hearing impairment.
Intractable & rare diseases researchImproving the Management of Patients with Hearing Loss by the Implementation of an NGS Panel in Clinical Practice.
GenesGenetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families.
Genes[Enlarged vestibular aqueduct syndrome-dehiscence syndromes-honeycomb mastoid : Pathophysiology and evidence for clinical differentiation].
HNOInsights into the pathophysiology of DFNA10 hearing loss associated with novel EYA4 variants.
Scientific reportsExome sequencing identifies PEX6 mutations in three cases diagnosed with Retinitis Pigmentosa and hearing impairment.
Molecular visionA novel variant in diaphanous homolog 1 (DIAPH1) as the cause of auditory neuropathy in a Chinese family.
International journal of pediatric otorhinolaryngologyClinical and genetic analysis of two wolfram syndrome families with high occurrence of wolfram syndrome and diabetes type II: a case report.
BMC medical geneticsNovel Loss-of-Function Variants in CDC14A are Associated with Recessive Sensorineural Hearing Loss in Iranian and Pakistani Patients.
International journal of molecular sciencesFirst-Line Molecular Genetic Evaluation of Autosomal Recessive Non-Syndromic Hearing Loss.
Turkish archives of otorhinolaryngologyRare KCNQ4 variants found in public databases underlie impaired channel activity that may contribute to hearing impairment.
Experimental & molecular medicineA novel mutation in PRPS1 causes X-linked Charcot-Marie-Tooth disease-5.
Neuropathology : official journal of the Japanese Society of NeuropathologyWhole-exome sequencing identifies a novel missense variant within LOXHD1 causing rare hearing loss in a Chinese family.
BMC medical geneticsMutation screening in non-syndromic hearing loss patients with cochlear implantation by massive parallel sequencing in Taiwan.
PloS oneLHFPL5 mutation: A rare cause of non-syndromic autosomal recessive hearing loss.
European journal of medical geneticsGenomic Landscape and Mutational Signatures of Deafness-Associated Genes.
American journal of human geneticsWhole exome sequencing in adult-onset hearing loss reveals a high load of predicted pathogenic variants in known deafness-associated genes and identifies new candidate genes.
BMC medical genomicsDe novo variants in GREB1L are associated with non-syndromic inner ear malformations and deafness.
Human geneticsGJB3/GJB6 screening in GJB2 carriers with idiopathic hearing loss: Is it necessary?
Journal of clinical laboratory analysisIdentification of a MYO7A mutation in a large Chinese DFNA11 family and genotype-phenotype review for DFNA11.
Acta oto-laryngologicaCommon founder effects of hereditary hemochromatosis, Wilson´s disease, the long QT syndrome and autosomal recessive deafness caused by two novel mutations in the WHRN and TMC1 genes.
HereditasA Novel Variant in SYNE4 Confirms its Causative Role in Sensorineural Hearing Loss.
Balkan medical journalWhole-exome sequencing to identify the cause of congenital sensorineural hearing loss in carriers of a heterozygous GJB2 mutation.
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck SurgeryThe genetic basis of deafness in populations of African descent.
Journal of genetics and genomics = Yi chuan xue baoAn example of the utility of genomic analysis for fast and accurate clinical diagnosis of complex rare phenotypes.
Orphanet journal of rare diseasesMutations in eight small DFNB genes are not a frequent cause of non-syndromic hereditary hearing loss in Czech patients.
International journal of pediatric otorhinolaryngology[Analysis common gene mutation spots of 127 non-syndromic deafness natients in Guangxi Drovince].
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgeryFerlins Show Tissue-Specific Expression and Segregate as Plasma Membrane/Late Endosomal or Trans-Golgi/Recycling Ferlins.
Traffic (Copenhagen, Denmark)Genomic copy number alterations in non-syndromic hearing loss.
Clinical geneticsCharacterising the spectrum of autosomal recessive hereditary hearing loss in Iran.
Journal of medical geneticsComprehensive genetic testing with ethnic-specific filtering by allele frequency in a Japanese hearing-loss population.
Clinical geneticsA comprehensive catalogue of the coding and non-coding transcripts of the human inner ear.
Hearing researchEPS8L2 is a new causal gene for childhood onset autosomal recessive progressive hearing loss.
Orphanet journal of rare diseasesMucolipidosis types II and III and non-syndromic stuttering are associated with different variants in the same genes.
European journal of human genetics : EJHGHigh prevalence of CDH23 mutations in patients with congenital high-frequency sporadic or recessively inherited hearing loss.
Orphanet journal of rare diseasesHomozygous TBC1D24 mutation in two siblings with familial infantile myoclonic epilepsy (FIME) and moderate intellectual disability.
Epilepsy researchOSBPL2 encodes a protein of inner and outer hair cell stereocilia and is mutated in autosomal dominant hearing loss (DFNA67).
Orphanet journal of rare diseasesNon-manifesting AHI1 truncations indicate localized loss-of-function tolerance in a severe Mendelian disease gene.
Human molecular geneticsAssociações
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É uma condição caracterizada por perda auditiva que não está associada a outros sinais de uma síndrome maior. Seu início costuma ocorrer no período neonatal ou na infância.
Referências
Fontes citadas no texto, publicações do grafo e bases de dados usadas neste verbete
8 publicações do grafo RarasNet (PubMed) · 6 bases de dados. Títulos, periódicos e PMIDs vêm direto da fonte, sem intermediação de IA.
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.
Citar este verbete
Raras. (s.d.). Surdez genética não sindrômica. Em Raras — Enciclopédia de Doenças Raras do Brasil. https://raras.org/doenca/surdez-genetica-nao-sindromica
Formato APA. Conteúdo sob CC BY 4.0 — reuso livre com atribuição.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
Surdez genética não sindrômica
📋 Origem dos dados
Esta página agrega dados de fontes públicas e oficiais. Dados sobre cobertura no SUS (PCDT, CEAF) são verificados ativamente por agente proativo (ver badge no infobox). Demais dados têm atribuição de fonte + data da última sincronização — clique para abrir o original.
- Doença rara (ontologia)
- fonte: Orphanet
- Identificador unificado
- fonte: MONDO
- Codificação WHO/SUS
- fonte: WHO ICD-10 / DATASUS
- CID-11 (futuro)
- fonte: WHO ICD-11
- NIH/GARD
- fonte: GARD (NIH)
- Indexação biomédica
- fonte: MeSH (NLM)
- Dado público estruturado
- fonte: Wikidata
