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Novel USH2A Mutations in Israeli Patients With Retinitis Pigmentosa and Usher Syndrome Type 2
Nadia Kaiserman, MSc;
Alexey Obolensky, MD, PhD;
Eyal Banin, MD, PhD;
Dror Sharon, PhD
Arch Ophthalmol. 2007;125(2):219-224.
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.
Clinical Relevance 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.
Author Affiliations: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
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