Point mutation in the MITF gene causing Waardenburg syndrome type II in a three-generation Indian family

Authors

  • Anil K. Lalwani,

    Corresponding author
    1. Laboratory of Molecular Otology, Epstein Laboratories, Department of Otolaryngology–Head and Neck Surgery, University of California San Francisco, San Francisco, California
    • Laboratory of Molecular Otology, Epstein Laboratories, Department of Otolaryngology–Head and Neck Surgery, 533 Parnassus Avenue, U490A, San Francisco, CA 94143-0526
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  • Ali Attaie,

    1. Laboratory of Molecular Otology, Epstein Laboratories, Department of Otolaryngology–Head and Neck Surgery, University of California San Francisco, San Francisco, California
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  • Frederick T. Randolph,

    1. Laboratory of Molecular Otology, Epstein Laboratories, Department of Otolaryngology–Head and Neck Surgery, University of California San Francisco, San Francisco, California
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  • Dilip Deshmukh,

    1. Rotary Deaf School, Ichalkaranji-Tilawani, District Kolhapur, Maharashtra, India
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  • Cynthia Wang,

    1. Laboratory of Molecular Otology, Epstein Laboratories, Department of Otolaryngology–Head and Neck Surgery, University of California San Francisco, San Francisco, California
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  • Anand Mhatre,

    1. Laboratory of Molecular Otology, Epstein Laboratories, Department of Otolaryngology–Head and Neck Surgery, University of California San Francisco, San Francisco, California
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  • Edward Wilcox

    1. Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland
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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. Am. J. Med. Genet. 80:406–409, 1998. © 1998 Wiley-Liss, Inc.

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