Novel USH2A mutations in Israeli patients with retinitis pigmentosa and Usher syndrome type 2.
OBJECTIVE
To identify USH2A mutations in Israeli patients with autosomal-recessive Usher syndrome type 2 (USH2) and retinitis pigmentosa (RP).


METHODS
Patients from 95 families with RP and 4 with USH2 were clinically evaluated. USH2A exons 2-72 were scanned for mutations using single-strand conformation and sequencing analyses. The frequency of novel missense changes was determined in patients and controls using restriction endonucleases.


RESULTS
The analysis revealed 3 USH2A mutations, 2 of which are novel, in 2 families with USH2 and a large family (MOL0051) with both USH2 and RP. Compound heterozygotes for 2 null mutations (Thr80fs and Arg737stop) in MOL0051 suffered from USH2 while compound heterozygotes for 1 of the null mutations and a novel missense mutation (Gly4674Arg) had nonsyndromic RP.


CONCLUSIONS
Our results support the involvement of USH2A in nonsyndromic RP and we report here of a second, novel, missense mutation in this gene causing autosomal-recessive RP.


CONCLUSIONS
Possible involvement of USH2A should be considered in the molecular genetic evaluation of patients with autosomal-recessive RP. Understanding the mechanism by which different USH2A mutations cause either USH2 or RP may assist in the development of novel therapeutic approaches.
Kaiserman
Nadia
N
Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
Obolensky
Alexey
A
Banin
Eyal
E
Sharon
Dror
D
D000328:Adult; D000368:Aged; D001299:Audiometry; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005091:Exons / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D007557:Israel / Q000453:epidemiology; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D012174:Retinitis Pigmentosa / Q000208:ethnology / Q000235:genetics*; D052245:Usher Syndromes / Q000208:ethnology / Q000235:genetics*; D058609:Visual Field Tests; D014794:Visual Fields
D016326:Extracellular Matrix Proteins; C112735:USH2A protein, human