Identification of novel USH2A mutations: Implications for the structure of USH2A protein

Bo Dreyer, Lisbeth Tranebjærg, Thomas Rosenberg, Michael D. Weston, William J. Kimberling, Øivind Nilssen

    Research output: Contribution to journalArticlepeer-review

    70 Scopus citations


    Usher syndrome type Il is an autosomal recessive disorder, characterised by stable hearing impairment from childhood and progressive retinitis pigmentosa from the late teens. Mutations in the USH2A gene, located on 1q41, were recently shown to be responsible for Usher syndrome type IIa. We have investigated the molecular pathology of Usher type II by screening the USH2A gene for mutations in 31 unrelated patients from Denmark and Norway. Besides the frequent 2299delG mutation, which accounted for 44% of the disease alleles, a heterogeneous spectrum of mutations was identified. Sixteen new, putative disease-causing mutations were detected, of which 12 were private and four were shared by unrelated patients. The disease-causing mutations were scattered throughout the gene and included six nonsense and seven missense mutations, two deletions and one small insertion. In addition, six non-pathogenic polymorphisms were identified. All missense mutations resulted in major amino acid side-chain alterations. Four missense mutations affected the N-terminal part of USH2A, whereas three missense mutations affected the laminin-type epidermal growth factor-like (LE) domain. The structural consequences of the mutations affecting the LE domain are discussed in relation to the three-dimensional structure of a LE-module of the mouse laminin γ1 chain.

    Original languageEnglish (US)
    Pages (from-to)500-506
    Number of pages7
    JournalEuropean Journal of Human Genetics
    Issue number7
    StatePublished - Jul 2000


    • Hearing impairment
    • Molecular modeling
    • Retinitis pigmentosa
    • Spectrum of mutations
    • Usher syndrome type II

    ASJC Scopus subject areas

    • Genetics
    • Genetics(clinical)


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