A novel mutation in COCH-implications for genotype-phenotype correlations in DFNA9 hearing loss

Michael S. Hildebrand, Luke Gandolfo, A. Eliot Shearer, Jennifer A. Webster, Maren Jensen, William J. Kimberling, Dietrich Stephan, Patrick L.M. Huygen, Richard J.H. Smith, Melanie Bahlo

    Research output: Contribution to journalArticlepeer-review

    20 Scopus citations

    Abstract

    Objectives/Hypothesis: To determine the cause of autosomal dominant hearing loss segregating in an American family. Study Design: Family study. Methods: Otologic and audiometric examination was performed on affected family members. Genome wide parametric multipoint linkage mapping using a dominant model was performed with Affymetrix 50K GeneChip data. Direct sequencing was used to confirm the causative mutation. Results: In American family 467, segregating autosomal dominant nonsyndromic hearing loss, a novel heterozygous missense mutation (c.362T>C; p.F121S) was identified in the COCH gene. This mutation was also associated with vestibular dysfunction typical of other DFNA9 families. However, affected family members also exhibited memory loss and night blindness. Conclusions: The novel COCH mutation affects the functionally important limulus factor C, Coch-5b2 and Lgl1 domain where most DFNA9 mutations have been localized. The onset of the hearing loss, in the 2nd or 3rd decade of life, is earlier than in most DFNA9 families. The progression of hearing loss and vestibular dysfunction in the American family is typical of other DFNA9 families with mutations in this domain. Memory loss and night blindness have not been previously reported in DFNA9 families.

    Original languageEnglish (US)
    Pages (from-to)2489-2493
    Number of pages5
    JournalLaryngoscope
    Volume120
    Issue number12
    DOIs
    StatePublished - Dec 2010

    Keywords

    • COCH gene
    • DFNA9
    • hearing loss
    • missense mutation
    • vestibular dysfunction

    ASJC Scopus subject areas

    • Otorhinolaryngology

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