title: A novel mutation in the MITF may be digenic with GJB2 mutations in a large Chinese family of Waardenburg syndrome type II.
abstract: Waardenburg syndrome type II (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.
authors.affiliation: Department of Otolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China.
authors.forename: Xukun
authors.initials: X
authors.lastname: Yan
authors.forename: Tianyu
authors.initials: T
authors.lastname: Zhang
authors.forename: Zhengmin
authors.initials: Z
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.forename: Duan
authors.initials: D
authors.lastname: Ma
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Huawei
authors.initials: H
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001299:Audiometry; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012335:RNA, Ribosomal / Q000235:genetics; D016415:Sequence Alignment; D014849:Waardenburg Syndrome / Q000235:genetics*; D055815:Young Adult
chemical_list: D017630:Connexins; D004272:DNA, Mitochondrial; C000607042:GJB2 protein, human; D051739:Microphthalmia-Associated Transcription Factor; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D000072259:Connexin 26