Missense mutation in the USH2A gene: association with recessive retinitis pigmentosa without hearing loss

Am J Hum Genet. 2000 Jun;66(6):1975-8. doi: 10.1086/302926. Epub 2000 Apr 20.


Microdeletions Glu767(1-bp del), Thr967(1-bp del), and Leu1446(2-bp del) in the human USH2A gene have been reported to cause Usher syndrome type II, a disorder characterized by retinitis pigmentosa (RP) and mild-to-severe hearing loss. Each of these three frameshift mutations is predicted to lead to an unstable mRNA transcript that, if translated, would result in a truncated protein lacking the carboxy terminus. Here, we report Cys759Phe, a novel missense mutation in this gene that changes an amino-acid residue within the fifth laminin-epidermal growth factor-like domain of the USH2A gene and that is associated with recessive RP without hearing loss. This single mutation was found in 4.5% of 224 patients with recessive RP, suggesting that USH2A could cause more cases of nonsyndromic recessive RP than does any other gene identified to date.

Publication types

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

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Base Sequence
  • Deafness*
  • Epidermal Growth Factor / chemistry
  • Extracellular Matrix Proteins / chemistry
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Genes, Recessive / genetics*
  • Humans
  • Laminin / chemistry
  • Male
  • Molecular Sequence Data
  • Mutation, Missense / genetics*
  • Pedigree
  • Protein Structure, Tertiary
  • Retinitis Pigmentosa / genetics*
  • Syndrome


  • Extracellular Matrix Proteins
  • Laminin
  • USH2A protein, human
  • Epidermal Growth Factor