摘要
Waardenburg syndrome typeⅡ(WS2) is associated with syndromic deafness.A subset of WS2,WS2A,accounting for approximately 15%of patients,is attributed to mutations in the microphthalmia-associated transcription factor(MITF) gene.We examined the genetic basis of WS2 in a large Chinese family.All 9 exons of the MITF gene,the single coding exon(exon 2) of the most common hereditary deafness gene GJB2 and the mitochondrial DNA(mtDNA) 12S rRNA were sequenced.A novel heterozygous mutation c.[742_743delAAinsT;746_747delCA]in exon 8 of the MITF gene co-segregates with WS2 in the family.The MITF mutation results in a premature termination codon and a truncated MITF protein with only 247 of the 419 wild type amino acids.The deaf proband had this MITF gene heterozygous mutation as well as a c.[109G〉A]+ [235delC]compound heterozygous pathogenic mutation in the GJB2 gene.No pathogenic mutation was found in mtDNA 12S rRNA in this family.Thus,a novel compound heterozygous mutation,c.[742_743delAAinsT;746_747delCA]in MITF exon 8 was the key genetic reason for WS2 in this family,and a digenic effect of MITF and GJB2 genes may contribute to deafness of the proband.
Waardenburg syndrome typeⅡ(WS2) is associated with syndromic deafness.A subset of WS2,WS2A,accounting for approximately 15%of patients,is attributed to mutations in the microphthalmia-associated transcription factor(MITF) gene.We examined the genetic basis of WS2 in a large Chinese family.All 9 exons of the MITF gene,the single coding exon(exon 2) of the most common hereditary deafness gene GJB2 and the mitochondrial DNA(mtDNA) 12S rRNA were sequenced.A novel heterozygous mutation c.[742_743delAAinsT;746_747delCA]in exon 8 of the MITF gene co-segregates with WS2 in the family.The MITF mutation results in a premature termination codon and a truncated MITF protein with only 247 of the 419 wild type amino acids.The deaf proband had this MITF gene heterozygous mutation as well as a c.[109G〉A]+ [235delC]compound heterozygous pathogenic mutation in the GJB2 gene.No pathogenic mutation was found in mtDNA 12S rRNA in this family.Thus,a novel compound heterozygous mutation,c.[742_743delAAinsT;746_747delCA]in MITF exon 8 was the key genetic reason for WS2 in this family,and a digenic effect of MITF and GJB2 genes may contribute to deafness of the proband.
基金
supported by the grants from the National Basic Research Program of China(Nos.2011CB504500, 2011CB504506 and 2010CB945503)
the National Basic Research Program of China(No.2011504502)
the Shanghai Municipal Commission of Science and Technology Program (No.09DJ140061)
the National Natural Science Foundation of China(No.81070793)