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 journalArticle

57 Citations (Scopus)

Abstract

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
Volume8
Issue number7
DOIs
StatePublished - Jul 1 2000

Fingerprint

Mutation
Missense Mutation
Usher Syndromes
Proteins
Genes
Retinitis Pigmentosa
Molecular Pathology
Laminin
Denmark
Norway
Hearing Loss
Epidermal Growth Factor
Alleles
Amino Acids

Keywords

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

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Dreyer, B., Tranebjærg, L., Rosenberg, T., Weston, M. D., Kimberling, W. J., & Nilssen, Ø. (2000). Identification of novel USH2A mutations: Implications for the structure of USH2A protein. European Journal of Human Genetics, 8(7), 500-506. https://doi.org/10.1038/sj.ejhg.5200491

Identification of novel USH2A mutations : Implications for the structure of USH2A protein. / Dreyer, Bo; Tranebjærg, Lisbeth; Rosenberg, Thomas; Weston, Michael D.; Kimberling, William J; Nilssen, Øivind.

In: European Journal of Human Genetics, Vol. 8, No. 7, 01.07.2000, p. 500-506.

Research output: Contribution to journalArticle

Dreyer, B, Tranebjærg, L, Rosenberg, T, Weston, MD, Kimberling, WJ & Nilssen, Ø 2000, 'Identification of novel USH2A mutations: Implications for the structure of USH2A protein', European Journal of Human Genetics, vol. 8, no. 7, pp. 500-506. https://doi.org/10.1038/sj.ejhg.5200491
Dreyer, Bo ; Tranebjærg, Lisbeth ; Rosenberg, Thomas ; Weston, Michael D. ; Kimberling, William J ; Nilssen, Øivind. / Identification of novel USH2A mutations : Implications for the structure of USH2A protein. In: European Journal of Human Genetics. 2000 ; Vol. 8, No. 7. pp. 500-506.
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