Genetic heterogeneity of usher syndrome: Analysis of 151 families with usher type I

Lisa M. Astuto, Michael D. Weston, Carol A. Carney, Denise M. Hoover, Cor W.R.J. Cremers, Mariette Wagenaar, Claes Moller, Richard J.H. Smith, Sandra Pieke-Dahl, Jacquie Greenberg, Raj Ramesar, Samuel G. Jacobson, Carmen Ayuso, John R. Heckenlively, Marta Tamayo, Michael B. Gorin, Willie Reardon, William J. Kimberling

    Research output: Contribution to journalArticlepeer-review

    62 Scopus citations

    Abstract

    Usher syndrome type I is an autosomal recessive disorder marked by hearing loss, vestibular areflexia, and retinitis pigmentosa. Six Usher I genetic subtypes at loci USH1A-USH1F have been reported. The MYO7A gene is responsible for USH1B, the most common subtype. In our analysis, 151 families with Usher I were screened by linkage and mutation analysis. MYO7A mutations were identified in 64 families with Usher L of the remaining 87 families, who were negative for MYO7A mutations, 54 were informative for linkage analysis and were screened with the remaining USH1 loci markers. Results of linkage and heterogeneity analyses showed no evidence of Usher types Ia or Ie. However, one maximum LOD score was observed lying within the USH1D region. Two lesser peak LOD scores were observed outside and between the putative regions for USH1D and USHIF, on chromosome 10. A HOMOG χ(2/(1)) plot shows evidence of heterogeneity across the USH1D, USH1F, and intervening regions. These results provide conclusive evidence that the second-most-common subtype of Usher I is due to genes on chromosome 10, and they confirm the existence of one Usher I gene in the previously defined USH1D region, as well as providing evidence for a second, and possibly a third, gene in the 10p/q region.

    Original languageEnglish (US)
    Pages (from-to)1569-1574
    Number of pages6
    JournalAmerican Journal of Human Genetics
    Volume67
    Issue number6
    DOIs
    StatePublished - 2000

    ASJC Scopus subject areas

    • Genetics
    • Genetics(clinical)

    Fingerprint

    Dive into the research topics of 'Genetic heterogeneity of usher syndrome: Analysis of 151 families with usher type I'. Together they form a unique fingerprint.

    Cite this