Variable hearing impairment in a DFNB2 family with a novel MYO7A missense mutation

M. S. Hildebrand, N. P. Thorne, C. J. Bromhead, K. Kahrizi, J. A. Webster, Z. Fattahi, M. Bataejad, W. J. Kimberling, D. Stephan, H. Najmabadi, M. Bahlo, R. J.H. Smith

    Research output: Contribution to journalArticlepeer-review

    35 Scopus citations

    Abstract

    Myosin VIIA mutations have been associated with non-syndromic hearing loss (DFNB2; DFNA11) and Usher syndrome type 1B (USH1B). We report clinical and genetic analyses of a consanguineous Iranian family segregating autosomal recessive non-syndromic hearing loss (ARNSHL). The hearing impairment was mapped to the DFNB2 locus using Affymetrix 50K GeneChips; direct sequencing of the MYO7A gene was completed. The Iranian family (L-1419) was shown to segregate a novel homozygous missense mutation (c.1184G>A) that results in a p.R395H amino acid substitution in the motor domain of the myosin VIIA protein. As one affected family member had significantly less severe hearing loss, we used a candidate approach to search for a genetic modifier. This novel MYO7A mutation is the first reported to cause DFNB2 in the Iranian population and this DFNB2 family is the first to be associated with a potential modifier. The absence of vestibular and retinal defects, and less severe low frequency hearing loss, is consistent with the phenotype of a recently reported Pakistani DFNB2 family. Thus, we conclude this family has non-syndromic hearing loss (DFNB2) rather than USH1B, providing further evidence that these two diseases represent discrete disorders.

    Original languageEnglish (US)
    Pages (from-to)563-571
    Number of pages9
    JournalClinical Genetics
    Volume77
    Issue number6
    DOIs
    StatePublished - Jun 2010

    Keywords

    • DFNB2
    • Genetic modifier
    • MYO7A gene
    • Missense mutation
    • Motor domain
    • Myosin VIIA protein
    • USH1B

    ASJC Scopus subject areas

    • Genetics
    • Genetics(clinical)

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