Mutation Screening Of SOX10 Gene In One Chinese Family With Waardenburg Syndrome Type 2

Waardenburg syndrome(WS) is an autosomal-dominant neural crest cell disorder phenotypically characterized by hearing impairment and disturbance of pigmentation.WS is an autosomal dominant disorder characterized by sensorineural hearing loss,pigmentary disturbances of the skin,hair,and iris,and other developmental defects.It is a clinically and genetically heterogeneous disease accounting for more than 2-5%of the congenitally deaf population.Not every patient with WS has all of the clinical manifestations of the disease;incomplete forms are common.There are four types of this syndrome,such as WSâ… (MIM 193500),WSâ…¡(MIM 193510),WSâ…¢(Klein-Waardenburg syndrome,MIM148820),WSâ…£(Waardenburg-Shah syndrome or Waardenburg-Hirschsprung disease,MIM 277580).Nowadays,great progress have been made in the genetic research of WS.The gene MITF,SNAI2 and SOX10 are responsible for WSâ…¡.Objiective:Comprehensive clinical analysis with two typical cases of Waardenburg syndrome typeâ…¡family and mutation detection for candidate gene MITF,SNAI2,SOX10.Then to WSâ…¡understand better and explore the molecular genetical mechanism of Waardenburg syndrome typeâ…¡.Methods:This study collected a Chinese family visited in the Outpatient Clinic of Otolaryngology in XiangYa Hospital.All participants gave their informed consent and collected blood samples prior to participation in this study.Clinic evaluation and diagonosis are conducted in the participation.And the proband was primarily defined as WSâ…¡.Genomic DNA was extracted from each individual and complete MITF,SNAI2,SOX10 gene coding exons were amplified by specific PCR primers.Direct sequencing was carried out to identify the mutations.The raw data was analyzed with Gene Tool software and molecular biological website.Results:(1) The patients were diagnosed as Waardenburg syndrome typeâ…¡.(2) we identified a heterozygous SOX10 frameshift mutation(c.l13delG) on exon 3 that is a frame shifting change with Glycine-38 as the first affected amino acid,changing to a Alanine and creating a new reading frame ending in a stop at position 71(p.Gly38AlafsX71).But the deletion mutation was not found in the normal individuals of the family and the 100 controls.The blood samples of MITF and SNAI2 genes were normal.Conclusions:(1) In this study,we have identified a novel deletion mutation in the sox10 gene in the two typical cases of Waardenburg syndrome typeâ…¡family.(2) The molecular findings provide better understanding of the function of sox10 gene and enrich the human gene mutation database.(3) More importantly,SOX10 deletions should be considered for first-step analysis in WS2,as well as MITF mutations. (4) The novel mutation provides an important basis for prenatal diagnosis.