In addition to hearing impairment, syndromic hearing impairment is often accompanied by disorders of urinary, skeletal, muscular, nervous, and ocular systems. Genetic factors have shown to play an important role in the pathogenesis of deafness. Mutations of X-linked genes may cause syndromic hearing impairment. Gene mapping, linkage analysis and next-generation sequencing may facilitate delineation of the pathogenesis of X-linked syndromic hearing impairment. This article reviews recent progress in molecular genetic research on X-linked syndromic hearing impairment, which may shed light for the diagnosis and treatment of these diseases.
Genetic Diseases, X-Linked ; genetics ; Genetic Research ; Hearing Loss ; diagnosis ; genetics ; therapy ; Humans ; Molecular Biology

Congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD) syndrome is a rare X-linked dominant and male-lethal multi-system disorder characterized by congenital hemidysplasia, strictly lateralized ichthyosiform nevus and ipsilateral limb defects. CHILD syndrome is caused by mutations of nicotinamide adenine dinucleotide phosphate steroid dehydrogenase-like protein (NSDHL) gene mapped to chromosome Xq28. The gene encodes 3β-hydroxylsterol dehydrogenase, which catalyses a step in the cholesterol biosynthetic pathway. This paper has provided a review for recent progress in research on CHILD syndrome including its clinical aspects, pathology, etiology, pathogenesis, differential diagnosis, and treatment, with a particular emphasis on its treatment..
Abnormalities, Multiple ; genetics ; Genetic Diseases, X-Linked ; genetics ; Humans ; Limb Deformities, Congenital ; genetics ; Nevus ; genetics ; Syndrome

5-Aminolevulinate Synthetase/genetics* ; Anemia, Sideroblastic/genetics* ; Genetic Diseases, X-Linked/genetics* ; Humans ; Mutation

Anemia, Sideroblastic ; diagnosis ; genetics ; Asian Continental Ancestry Group ; Genetic Diseases, X-Linked ; diagnosis ; genetics ; Humans ; Pedigree

OBJECTIVE: To explore the genetic pathogenesis of X-linked agammaglobulinemia in two patients for clinical diagnosis and family counseling. METHODS: Data was collected from the patients' family including clinical information, blood immunoglobulin level, as well as classification and subgrouping of B lymphocytes. Gene mutations were screened by whole exome sequencing (WES) through next-generation sequencing (NGS), the result was verified with Sanger sequencing. RESULTS: A BTK c.1627T>C (p.Ser543Pro) variant was found in the pedigree. The phenotype and variant have co-segregated in the pedigree. The variant was not found in population database. The variant has affected in the kinase domain which contained no benign variants and is harmful as predicted through bioinformatic analysis. CONCLUSION BTK c.1627T>C (p.Ser543Pro) is a pathogenic variant contributing to X-linked agammaglobulinemia in this pedigree. Above finding has provided reproduction guidance for this family.
Agammaglobulinaemia Tyrosine Kinase/genetics* ; Agammaglobulinemia/genetics* ; DNA Mutational Analysis ; Genetic Diseases, X-Linked ; Humans ; Mutation ; Pedigree

OBJECTIVE: To explore the genetic basis for a EAST/SeSAME syndrome child featuring epilepsy, ataxia, sensorineural deafness and intellectual disability. METHODS: A child with EAST/SeSAME syndrome who had presented at the Third Affiliated Hospital of Zhengzhou University in January 2021 was selected as the study object. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. RESULTS: Genetic testing revealed that the child has harbored compound heterozygous variants of the KCNJ10 gene, namely c.557T>C (p.Val186Ala) and c.386T>A (p.Ile129Asn), which were inherited from her mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted as likely pathogenic (PM1+PM2_Supporting+PP3+PP4; PM1+PM2_Supporting+PM3+PP3+PP4). CONCLUSION The patient was diagnosed with EAST/SeSAME syndrome due to the compound heterozygous variants of the KCNJ10 gene.
Humans ; Child ; Female ; Intellectual Disability/genetics* ; Hearing Loss, Sensorineural/genetics* ; Ataxia ; Genetic Diseases, X-Linked ; Mutation

OBJECTIVETo study the clinical manifestations and identify causative mutations for a Chinese family affected with X-linked Charcot-Marie-Tooth disease.

METHODSClinical, electrophysiological and pathological features of the family were carefully analyzed by neurologists. Blood samples were obtained from the proband and other family members. Genomic DNA was extracted. Mutation analysis of GJB1 gene was analyzed with PCR and direct sequencing.

RESULTSThe family has fit with X-linked inheritance, and the affected individuals have typical clinical manifestations. A c.614A>G (p.Asn205Ser) mutation was detected in the GJB1 gene in all affected individuals in the family.

CONCLUSIONA c.614A>G (p.Asn205Ser) mutation of GJB1 gene is co-segregated with the disease phenotype in this family and probably underlies the disease.

Asian Continental Ancestry Group ; genetics ; Charcot-Marie-Tooth Disease ; genetics ; Child ; Connexins ; genetics ; Female ; Genes, X-Linked ; genetics ; Genetic Diseases, X-Linked ; genetics ; Humans ; Male ; Mutation ; Pedigree

OBJECTIVE: To explore the genetic basis for a child affected with cerebral creatine deficiency syndrome 1 (CCDS1). METHODS: High-throughput sequencing was carried out to screen pathogenic variant associated with the clinical phenotype of the proband. The candidate variant was verified by Sanger sequencing. RESULTS: High-throughput sequencing revealed that the proband has carried heterozygous c.327delG variant of the SLC6A8 gene, which was verified by Sanger sequencing.Neither parent was found to carry the same variant. CONCLUSION The de novo heterozygous c.327delG variant of the SLC6A8 gene probably underlay the CCDS1 in this child.
Brain Diseases, Metabolic, Inborn/genetics* ; Creatine ; Genetic Testing ; Heterozygote ; Humans ; Mental Retardation, X-Linked ; Mutation

OBJECTIVE: To explore the genetic basis for a pedigree affected with Nance-Horan syndrome. METHODS: Clinical manifestation of the patients was analyzed. Genomic DNA was extracted from peripheral blood samples of the pedigree members and 100 unrelated healthy controls. A panel of genes for congenital cataract was subjected to next-generation sequencing (NGS), and candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of American College of Medical Genetics and Genomics (ACMG). mRNA expression was determined by reverse transcriptase-PCR (RT-PCR). Linkage analysis based on short tandem repeats was carried out to confirm the consanguinity. RESULTS: A small insertional variant c.766dupC (p.Leu256Profs*21) of the NHS gene was identified in the proband and his affected mother, but not among unaffected members and the 100 healthy controls. The variant was unreported in Human Gene Mutation Database (HGMD) and other databases. Based on the ACMG guideline, the variant is predicted to be pathogenic (PVS1+PM2+PM6+PP4). CONCLUSION The novel variant c.766dupC of the NHS gene probably underlay the X-linked dominant Nance-Horan syndrome in this pedigree.
Cataract/genetics* ; Genetic Diseases, X-Linked ; Humans ; Mutation ; Pedigree ; State Medicine ; Tooth Abnormalities

OBJECTIVE: To investigate the gene mutation of patients with WAS gene defect and its correlation with clinical manifestations. METHODS: Thirty-one patients consulted in Children's Hospital of Soochow University from January 2013 to February 2018 were enrolled in this study. The hot pot mutations of WAS gene in 31 patients were detected and related clinical phenotypes were analyzed retrospectively. RESULTS: All patients were male. The median onset age was 1 month (range, 0-83 months). Nine mutants were reported as novel mutations among 25 mutants detected in 31 patients, including c.1234_1235dupCC, c.1093-1097delG, c.28-30dupC, c.436G>T, c.273 + 10_273 + 11dupCC, c.995_996insG, c.1010T>A, c.332_333delCC and c.683C>T mutations. There were 25 cases of classic WAS which mutations included missense mutation, deletion mutation, insertion mutation, splicing mutation and nonsense mutation, 2 cases of X-linked thrombocytopenia (XLT) were induced by missense mutation, 1 case of intermittent X-linked thrombocytopenia (IXLT) was induced by splicing mutation, 2 cases of X-linked pancytopenia were induced by missense mutation. Intravenous immunoglobulin (IVIG) and glucocorticoid therapy in IXLT patient was effective, and remission could be sustained, platelets could be increased in the short-term in treated XLT patients, but only a small part of classic WAS patients(8.0%) showed transient response to it, the IVIG and glucocorticoid therapy did not improve the status of platelet in XLP patients. Immune laboratory examination showed that CD3 was decreased in 60.0% patients, CD19 was decreased in 12.0% patients, and CD56CD16 in 4 patients was decreased, accounting for 16.0%. Out of 24 patients, 22 patients were alive after treated with hematopoietic stem cell transplantation (HSCT), 4 patients who were not given HSCT died of brain bleeding and severe infection, 1 patient diagnosed as IXLT got remission and survived. CONCLUSION WAS gene defect is an important basis for the diagnosis of WAS and related diseases. IVIG plus glucocorticoid therapy is less effective for fewer patients, the HSCT is an effective treatment for WAS.
Genetic Diseases, X-Linked ; Humans ; Male ; Mutation ; Phenotype ; Retrospective Studies ; Thrombocytopenia ; Wiskott-Aldrich Syndrome Protein ; genetics