title: A de novo deletion mutation in SOX10 in a Chinese family with Waardenburg syndrome type 4.
abstract: Waardenburg syndrome type 4 (WS4) or Waardenburg-Shah syndrome is a rare genetic disorder with a prevalence of <1/1,000,000 and characterized by the association of congenital sensorineural hearing loss, pigmentary abnormalities, and intestinal aganglionosis. There are three types of WS4 (WS4A-C) caused by mutations in endothelin receptor type B, endothelin 3, and SRY-box 10 (SOX10), respectively. This study investigated a genetic mutation in a Chinese family with one WS4 patient in order to improve genetic counselling. Genomic DNA was extracted, and mutation analysis of the three WS4 related genes was performed using Sanger sequencing. We detected a de novo heterozygous deletion mutation [c.1333delT (p.Ser445Glnfs*57)] in SOX10 in the patient; however, this mutation was absent in the unaffected parents and 40 ethnicity matched healthy controls. Subsequent phylogenetic analysis and three-dimensional modelling of the SOX10 protein confirmed that the c.1333delT heterozygous mutation was pathogenic, indicating that this mutation might constitute a candidate disease-causing mutation.
authors.affiliation: Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yaowu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Na
authors.initials: N
authors.lastname: Shen
authors.affiliation: Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Haiyi
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Lu
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D005190:Family; D006239:Haplotypes / Q000235:genetics; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D010334:Paternity; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055757:SOXE Transcription Factors / Q000737:chemistry / Q000235:genetics*; D014849:Waardenburg Syndrome / Q000235:genetics*
chemical_list: C527923:SOX10 protein, human; D055757:SOXE Transcription Factors