title: Missense mutation in the USH2A gene: association with recessive retinitis pigmentosa without hearing loss.
abstract: 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.
authors.affiliation: Ocular Molecular Genetics Institute and the Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, 02114, USA.
authors.forename: C
authors.initials: C
authors.lastname: Rivolta
authors.forename: E A
authors.initials: EA
authors.lastname: Sweklo
authors.forename: E L
authors.initials: EL
authors.lastname: Berson
authors.forename: T P
authors.initials: TP
authors.lastname: Dryja
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D003638:Deafness; D004815:Epidermal Growth Factor / Q000737:chemistry; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D006801:Humans; D007797:Laminin / Q000737:chemistry; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D017434:Protein Structure, Tertiary; D012174:Retinitis Pigmentosa / Q000235:genetics*; D013577:Syndrome
chemical_list: D016326:Extracellular Matrix Proteins; D007797:Laminin; C112735:USH2A protein, human; D004815:Epidermal Growth Factor