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

Eur J Hum Genet. 2000 Jul;8(7):500-6. doi: 10.1038/sj.ejhg.5200491.


Usher syndrome type II 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 gamma1 chain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • DNA Primers / chemistry
  • Deafness / genetics*
  • Extracellular Matrix Proteins / chemistry
  • Extracellular Matrix Proteins / genetics*
  • Genetic Variation
  • Humans
  • Laminin / chemistry
  • Laminin / metabolism
  • Models, Molecular
  • Models, Structural
  • Molecular Sequence Data
  • Mutation, Missense
  • Protein Conformation
  • Retinitis Pigmentosa / genetics*
  • Sequence Homology, Amino Acid
  • Syndrome


  • DNA Primers
  • Extracellular Matrix Proteins
  • Laminin
  • USH2A protein, human
  • Ush2a protein, mouse