Turner syndrome (TS) is a common chromosomal abnormality caused by the complete or partial absence of one X chromosome. It affects approximately 1 in ~ 1,200 to 2,500 female births. In this case report, we examined the clinical details of a 21-year-old female for cytogenetic investigation due to the absence of menarche (primary amenorrhea). Karyotype analysis revealed [46,X, del(X)(q24)[22]/45,X[28]], representing a mosaic form of TS with a novel deletion of the long arm of the X chromosome. This case demonstrates that TS variants may present with menstrual disorder in the absence of typical dysmorphic features. Further investigation into rare TS variants in females lacking standard features is crucial for understanding genotype-phenotype correlations in TS.

Turner syndrome is a complicated gonadal insufficiency, infertility, and endocrine disease caused by the partial to complete loss of one X chromosome. Women with Turner syndrome have been reported to show altered effector T-cell subgroups; however, the relationship between T-cell subgroups and chromosome type remains unknown. In this study, we investigated immune abnormalities and karyotypes of Turner syndrome. Using flowcytometry, we examined the T-cell subsets of 20 women with Turner syndrome and 23 women serving as controls (without recurrent pregnancy loss), between July 2021 and June 2022. Background data of the women with Turner syndrome were also collected. Significantly lower levels of helper T-cells 1 and 2 were observed in women with Turner syndrome than in the control group (4.5 ± 2.88 vs. 8.54 ± 4.45, p < 0.05, 0.56 ± 0.38 vs. 0.97 ± 0.48, p < 0.05, respectively). With respect to karyotypes, deletion of a specific region, pseudoautosomal region 2, which typically escapes X-inactivation, might influence regulatory T cells (Treg) levels as copy number of PAR2 and Treg rate were positively correlated (r = 0.76). Individuals with Turner syndrome showed an altered T-cell subset, which might be caused by the deletion of a specific part of the X chromosome, pseudoautosomal region 2. This finding suggests that women with Turner syndrome in a specific karyotype show altered T-cell subsets, and more cases are needed to determine whether these T-cell changes could influence pregnancy outcomes.

Turner syndrome (TS), also known as congenital ovarian hypoplasia, is one of the most common sex chromosome diseases in women. It is caused by the complete or partial deletion or structural change of one X chromosome in all or part of somatic cells. A rare case of karyotype Turner syndrome is reported. A 16-year-old female presented with oligomenorrhea and a history of menstrual irregularities. Menarche occurred at age 14, followed by only one menstrual period in the same year. Her second menstruation occurred a year later at age 15, with no menstruation thereafter. Peripheral venous blood was collected after obtaining informed consent. Routine lymphocyte culture and G-banding analysis revealed mosaic karyotypes: 44,X, der(21;22)(q10;q10)[43]/45,XX,der(21;22)(q10;q10)[27]. Menstrual disorders are very common nowadays and generally related to personal stress, endocrine system, etc., and may also be related to sex chromosomes. This case is caused by the abnormal structure and number of sex chromosomes.

Complex glycerol kinase deficiency (CGKD), also known as Xp21 contiguous gene deletion syndrome, is a rare X-linked recessive disorder resulting from partial deletion of the Xp21.3 chromosomal region. CGKD encompasses several loci, including glycerol kinase (GK), Duchenne muscular dystrophy (DMD), X-linked adrenal hypoplasia congenita (NR0B1), and intellectual developmental disorder (IL1RAPL1). We present the cases of two male siblings diagnosed with CGKD. The elder sibling was initially suspected of having congenital adrenal hypoplasia (CAH). Whole exome sequencing (WES) revealed an interstitial deletion of 6.6 Mb on Xp21.3p21.1, encompassing critical genes including GK, DMD, NR0B1, and IL1RAPL1. The younger sibling was diagnosed shortly after birth based on family history, clinical and biochemical findings. The presented report highlights the diagnostic challenges associated with CGKD and the important role of genetic testing in confirming the diagnosis. A multidisciplinary team approach is necessary. Diagnosing Complex Glycerol Kinase Deficiency: A Case Study of Two Brothers Complex Glycerol Kinase Deficiency (CGKD) is a rare, inherited condition caused by the deletion of a group of genes on the X chromosome, affecting various systems in the body, such as muscles, hormone regulation, and development. Diagnosing CGKD is challenging due to its diverse and complex symptoms, as illustrated in this case of two brothers. The older sibling showed early signs of adrenal insufficiency, including poor feeding, vomiting, and abnormal skin pigmentation, and was initially misdiagnosed with a more common adrenal condition. Genetic testing later confirmed CGKD through the identification of a specific X chromosome deletion. This delayed diagnosis emphasizes the need to consider rare genetic disorders when symptoms are atypical. The younger brother was diagnosed at birth through family history, clinical evaluations, and genetic testing, enabling early management with hormone replacement therapy and dietary adjustments. Both children are now supported by a multidisciplinary team, addressing their medical, developmental, and nutritional needs, which has improved their health and quality of life. This case highlights the importance of genetic testing in diagnosing CGKD, especially in cases of unexplained developmental delay and adrenal insufficiency, as early detection allows for better management and family support.

Turner syndrome is a chromosomal disorder, characterized by the partial or total deletion of one X chromosome, resulting in various karyotypes that presumably lead to different phenotypes. However, most studies find it difficult to predict phenotypes from karyotypes due to the presence of mosaicism. The purpose of this study is to clarify the relationship between karyotype and phenotype in Turner syndrome with non-mosaic X chromosome structural rearrangements. A systematic literature search was conducted using Medline and Embase classics plus Embase between 1947 and September 2023. A total of 487 Turner women with non-mosaic X chromosome structural rearrangements were included from the 69 studies. The prevalence of short stature was 72.4% in Turner syndrome with non-mosaic X chromosome structural rearrangements, 80.1% in the short arm deletion group (del (Xp)), 75% in the del(X)(p22.3) group, 65.8% in the del(X)(p21) and del(X)(p22) group, and 37.5% (20%-66.7%) in the long arm deletion group (del(Xq)). The prevalence of ovarian dysfunction was 78.8% in Turner syndrome with non-mosaic X chromosome structural rearrangements, 72.5% in the del (Xp) group, 27.6% in the del (X)(p22.3) group, 33.3% in the del (X)(p21) and del(X)(p22) group, and 94.6% in the del (Xq) group. The recognition of X chromosome breakpoints is useful in the management of Turner syndrome complications, since some phenotypes are unique depending on the deletion region. Ovarian dysfunction is significantly related to karyotype, so the identification of karyotypes in Turner syndrome is important for managing ovarian dysfunction and predicting future fertility. The Kell blood group system is vast, with 38 blood group antigens. The Kell system is notorious for its immunogenicity, which is third after ABO and Rhesus D. This system is involved in severe forms of hemolytic disease of the fetus and newborn and hemolytic transfusion reactions. Further, this blood group system is associated with chronic granulomatous diseases and a multisystem syndrome involving neurological, cardiovascular, and hematologic symptoms called McLeod syndrome. The symbol of the Kell blood group system as per "International Society of Blood Transfusion" (ISBT) is KEL; ISBT number: 006. History: The Kell blood group system was described in 1946 and named after Mrs Kelleher, whose newborn child died of hemolytic disease of fetus and newborn (HDFN) due to an antibody against his red blood cells (RBCs). This antibody also reacted with her daughter's and husband's RBCs and was named anti-K. Later, its antithetical antigen k was discovered in 1949, and the null phenotype (K0) in 1957. Genetics: The KEL gene encodes the Kell antigens and is located at chromosome 7q34, comprising 20 exons spanning 21.25 kb of genomic DNA. This gene is also known as Kell metallo-endopeptidase, ECE3, or CD238. Single nucleotide polymorphisms are responsible for multiple Kell antigens. Another important XK gene required for the expression of Kell antigen is present on the short arm of chromosome X (Xp21.1) and is responsible for forming the Kx antigen. Structure of Kell glycoprotein: The KEL gene encodes the polymorphic Kell and para-Kell glycoproteins, structurally single-pass RBC membrane proteins, or type II glycoproteins. The N terminal is intracytoplasmic, and the C terminal is multi-folded, bound by disulfide bonds, and extracytoplasmic. They constitute around 732 amino acids; mutations in these lead to the formation of a multitude of Kell antigens. The Kell glycoprotein is covalently linked to the Kx protein via a single disulfide bond. This Kx antigen protein traverses the RBC membrane 10 times. The absence of Kx protein leads to McLeod syndrome. The Kell glycoproteins have been found to have a similar sequence as the neprilysin (M13) family of zinc endopeptidases and, hence, act like proteolytic enzymes. They share a pentameric sequence HEXXH, which is needed to add zinc and proteolytic activity. Kell preferentially cleaves big endothelin-3, converting it to the bioactive peptide endothelin-3. This potent vasoconstrictor peptide leads to vascular endothelial growth factor formation. Antigens: The Kell system is highly polymorphic, consisting of 38 different blood group antigens. The Kell antigens are found on erythroid cells and progenitor myeloid cells and are also present in skeletal muscles and testes. Common Kell Antigens K antigen: ISBT symbol: KEL1. ISBT number: 006.001. Low prevalence antigen. Antithetical antigen: k (KEL 2). Cord RBCs: Expressed. The K antigen is detected on fetal RBCs as early as the tenth gestational week and is well-developed at birth. The KEL1 antigen is strongly immunogenic after the Rh blood group system. Study results have reported that every 1 out of 10 Kell antigen-negative individuals transfused with Kell antigen-positive donor red cells can develop anti-K antibodies after transfusion. The K antigen is not denatured by the enzymes ficin and papain but is destroyed by combined trypsin and chymotrypsin. Additionally, dithiothreitol (DTT), 2-mercaptoethanol, 2-aminoethylisothiouronium bromide, and ZZAP (mixture of a sulfhydryl reagent [dithiothreitol] and a proteolytic enzyme [papain or ficin]) can also destroy the Kell antigen. DTT, a reducing agent, interferes with the disulfide bonds between amino acids essential for the structural integrity of specific proteins and maintaining the pentameric structure of immunoglobulin (Ig) M molecules. Treating RBCs with DTT can denature other blood group antigens, including Kell, Lutheran, Yt, John Milton Hagen (JMH), Landsteiner-Wiener (LW), Cromer, Indian, Dombrock, and Knops systems—potentially impacting the recognition of these antigens by their specific antibodies. k (Cellano) antigen: ISBT symbol: KEL2. Formerly termed as Cellano. ISBT number: 006.002. High prevalence antigen. Antithetical antigen: K (KEL1). Cord RBCs: Expressed. Detected as early as seven weeks of gestation. Resistance and sensitivity to enzymes and chemicals are the same as those of KEL1. Kpa antigen: ISBT symbol: KEL3. ISBT number: 006.003. Low prevalence antigen. Antithetical antigen: Kpb (KEL4) Kpc (KEL21). Cord RBCs: Expressed. Resistant to enzymes (ficin, papain, chymotrypsin). Kpb antigen: ISBT symbol: KEL4. ISBT number: 006.004. High prevalence antigen. Antithetical antigen: Kpa (KEL3) Kpc (KEL21). Cord RBC's: Expressed. Resistant to enzymes (ficin, papain, chymotrypsin). Jsa antigen: ISBT symbol: KEL6. ISBT number: 006.006. Low prevalence antigen. Antithetical antigen: Jsb (KEL7). Cord RBCs: Expressed. Resistant to enzymes (ficin, papain, chymotrypsin). Jsb antigen: ISBT symbol: KEL7. ISBT number: 006.007. High prevalence antigen. Antithetical antigen: Jsa (KEL6). Cord RBC: Expressed. Resistant to enzymes (ficin, papain, chymotrypsin). Other rare Kell antigens These are further divided as high and low-prevalence antigens: High prevalence antigens: Ku (KEL5), KEL11, KEL12, KEL13, KEL14, KEL16, KEL18, KEL19, Km (KEL20), KEL22, TOU (KEL26), RAZ (KEL27), KALT (KEL29), KTIM (KEL30), KUCI (KEL32), KANT (KEL33), KASH (KEL34), KELP (KEL35), KETI (KEL36), KHUL(KEL37), KYOR(KEL38), KEL40 Low prevalence antigens: Ula (KEL10), Wka (KEL17), KEL21, KEL23, KEL24, VLAN (KEL25), VONG (KEL28), KYO (KEL31), KEAL (KEL39), KEL41 Antibodies of the Kell Blood Group System Anti-K antibodies, commonly IgG antibodies, do not bind complement and mostly react at 37 °C with the anti-human globulin (AHG) phase. Anti-K antibodies can also react at room temperature in the saline phase if they are IgM-type; they are usually formed in response to exposure following pregnancy or transfusion, but some examples of naturally occurring anti-K can also be seen. These IgM antibodies have been found in patients with Escherichia coli infections, which disappear after recovery. Anti-K antibodies may show depressed reactivity with some low–ionic-strength solution reagents, so an AHG phase is required to detect these antibodies. Anti-K has been implicated in severe hemolytic transfusion reactions and HDFN. If a patient develops antibodies to high-prevalence Kell antigens like k, it is challenging to find compatible units due to the low percentage of antigen-negative donors; antibody formation is rare due to its high prevalence. Identifying antibodies against low-prevalence antigens is difficult as their corresponding antigens are not included in antibody identification panels, which can rarely present as unexpected HDFN or transfusion reactions (see Table. Kell Blood Group Frequencies in Different Populations by Percentage). Anti-K will react well with K+k+ and K+k− red cells in antibody panels, showing no dosage phenomena. A rare case report of anti-Jsb was found in the Nigerian population, where this antibody was associated with decreased red cell survival.  Uncommon Kell Phenotypes K0 phenotype and anti-Ku antibody: K0 or Kell null phenotype was identified by Chown et al in 1957, and it lacks all Kell antigens on the RBCs. The Kell null phenotype shows a prevalence of 0.001% except in populations of Finland and Japan. These individuals show the inheritance of 2 recessive K0 genes in homozygotes (K0 K0). The absent antigens do not cause any functional abnormality in these RBCs. The alloantibody in K0 individuals post-transfusion has been called anti-Ku (anti-KEL5), which is clinically significant. These recipients should only be transfused with the K0 red cell type. One case report shows that anti-Ku specificity and anti-H were also identified in co-trimoxazole (trimethoprim and sulfamethoxazole) dependent antibodies. If there is a diminished presence of Kell antigens in place of complete absence, the phenotype is called Kmod. This is due to multiple missense mutations in the glycoprotein. Both K0 and Kmod show increased Kx protein. Kmod individuals may also form anti-Ku-type antibodies, but neither are similar.  McLeod phenotype: This rare phenotype occurs due to the absence of the Kx protein. Kell glycoprotein is covalently linked to Kx protein by a single disulfide bond, and hence, in its absence, it lacks a high prevalence Kell antigen and has depression of the rest. Individuals with this phenotype develop a neuromuscular syndrome, McLeod syndrome. This condition is an X-linked recessive disorder where females are carriers and males are affected. At the molecular level, it can be due to a hemizygous XK pathogenic variant (90%) or a hemizygous deletion of Xp21.1 (10%). The Kell blood group system antigens are expressed weakly in individuals with McLeod syndrome, except for the Km antigen (KEL20), which is absent. The XK gene encodes a protein that helps properly express antigens of the Kell blood group system on the RBC surface. When this gene is mutated, it leads to the functional ineffectiveness of the Kell antigens. Depressed Kell antigen (Cellano) in Gerbich-negative phenotypes: Both Muller and Debien reported reduced expression of 'k' antigens in RBCs of Gerbich group-negative phenotype (Ge:-2,-3) in individuals using monoclonal anti-k. This may be due to conformational changes in epitopes of the Kell blood group system, which shift the protein 4.1 complex to proteins like glycophorin C in the RBC membrane.  Lab method for Kell blood group determination Determining the Kell blood group involves various methodologies, each with advantages and limitations. These methods can be broadly categorized into serological and molecular techniques. In serological methods, hemagglutination tests such as forward typing are commonly used to detect the presence of Kell antigens on RBCs by utilizing specific antibodies like anti-K. Agglutination indicates the presence of the K antigen, while a lack of agglutination suggests its absence. Although this method is rapid and straightforward, it may lack sensitivity for weakly expressed antigens, particularly in partial or weak Kell phenotypes. Reverse typing involves testing the serum for anti-K antibodies to confirm the results of forward typing, which is crucial for ensuring accurate blood typing before transfusions. This step helps identify any unexpected antibodies that could lead to transfusion reactions. Another technique, gel centrifugation, employs a gel medium to separate agglutinated from non-agglutinated cells, thereby improving sensitivity and specificity. This method is particularly beneficial in reducing false-negative results and is often used in blood banks for routine testing. In molecular methods, polymerase chain reaction (PCR)-based techniques are highly sensitive and detect specific genotypes associated with Kell antigens. This approach is particularly useful in cases where serological methods may fail, such as in patients with autoimmune hemolytic anemia or those who have been recently transfused, as these conditions can obscure antigen expression. PCR with sequence-specific primers (PCR-SSP) enables the determination of specific alleles associated with Kell antigens; this is both cost-effective and reliable, making it suitable for routine testing in blood banks. This method can also identify rare phenotypes that may not be detected through serological means. PCR with restriction fragment length polymorphism (PCR-RFLP) analyzes variations in DNA sequences corresponding to different Kell antigens, providing detailed genetic information about blood group polymorphisms. This level of detail can be crucial for understanding compatibility in transfusions and organ transplants. Microarray technology, which can simultaneously analyze multiple blood group antigens, including Kell, is highly efficient for large-scale screenings and provides comprehensive data on various blood group systems. This method allows for rapid screening of donors and patients alike, facilitating better matching processes.