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.
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.
Authors: Elena Aller; Lise Larrieu; Teresa Jaijo; David Baux; Carmen Espinós; Fernando González-Candelas; Carmen Nájera; Francesc Palau; Mireille Claustres; Anne-Françoise Roux; José M Millán Journal: Eur J Hum Genet Date: 2010-02-10 Impact factor: 4.246
Authors: Jacque L Duncan; Wendi Liang; Maureen G Maguire; Isabelle Audo; Allison R Ayala; David G Birch; Joseph Carroll; Janet K Cheetham; Simona Degli Esposti; Todd A Durham; Laura Erker; Sina Farsiu; Frederick L Ferris; Elise Heon; Robert B Hufnagel; Alessandro Iannaccone; Glenn J Jaffe; Christine N Kay; Michel Michaelides; Mark E Pennesi; José-Alain Sahel Journal: Am J Ophthalmol Date: 2020-05-22 Impact factor: 5.488
Authors: Ferry Fj Kersten; Erwin van Wijk; Lisette Hetterschijt; Katharina Bauβ; Theo A Peters; Mariam G Aslanyan; Bert van der Zwaag; Uwe Wolfrum; Jan Ee Keunen; Ronald Roepman; Hannie Kremer Journal: Cilia Date: 2012-04-25
Authors: Alessandro Iannaccone; Carmen C Brewer; Peiyao Cheng; Jacque L Duncan; Maureen G Maguire; Isabelle Audo; Allison R Ayala; Paul S Bernstein; Gavin M Bidelman; Janet K Cheetham; Richard L Doty; Todd A Durham; Robert B Hufnagel; Mark H Myers; Katarina Stingl; Wadih M Zein Journal: Am J Med Genet A Date: 2021-07-30 Impact factor: 2.578