title: Point mutation in the MITF gene causing Waardenburg syndrome type II in a three-generation Indian family.
abstract: Waardenburg syndrome (WS) is an autosomal-dominant neural crest cell disorder phenotypically characterized by hearing impairment and disturbance of pigmentation. A presence of dystopia canthorum is indicative of WS type 1, caused by loss of function mutation in the PAX3 gene. In contrast, type 2 WS (WS2) is characterized by normally placed medial canthi and is genetically heterogeneous; mutations in MITF (microphthalmia associated transcription factor) associated with WS2 have been identified in some but not all affected families. Here, we report on a three-generation Indian family with a point mutation in the MITF gene causing WS2. This mutation, initially reported in a Northern European family, creates a stop codon in exon 7 and is predicted to result in a truncated protein lacking the HLH-Zip or Zip structure necessary for normal interaction with its target DNA motif. Comparison of the phenotype between the two families demonstrates a significant difference in pigmentary disturbance of the eye. This family, with the first documented case of two unrelated WS2 families harboring identical mutations, provides additional evidence for the importance of genetic background on the clinical phenotype.
authors.affiliation: Epstein Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, 94143-0526, USA. lalwani@itsa.ucsf.edu
authors.forename: A K
authors.initials: AK
authors.lastname: Lalwani
authors.forename: A
authors.initials: A
authors.lastname: Attaie
authors.forename: F T
authors.initials: FT
authors.lastname: Randolph
authors.forename: D
authors.initials: D
authors.lastname: Deshmukh
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Mhatre
authors.forename: E
authors.initials: E
authors.lastname: Wilcox
mesh_terms: D001483:Base Sequence; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005192:Family Health; D005260:Female; D005796:Genes / Q000235:genetics*; D006801:Humans; D007194:India; D008126:Lod Score; D008297:Male; D051739:Microphthalmia-Associated Transcription Factor; D010375:Pedigree; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D014157:Transcription Factors; D014849:Waardenburg Syndrome / Q000235:genetics* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D014157:Transcription Factors