%0 Journal Article %J Genet Med %D 2015 %T Two specific mutations are prevalent causes of recessive retinitis pigmentosa in North American patients of Jewish ancestry. %A Venturini, Giulia %A Koskiniemi-Kuendig, Hanna %A Harper, Shyana %A Berson, Eliot L %A Rivolta, Carlo %X

PURPOSE: Retinitis pigmentosa is a Mendelian disease with a very elevated genetic heterogeneity. Most mutations are responsible for less than 1% of cases, making molecular diagnosis a multigene screening procedure. In this study, we assessed whether direct testing of specific alleles could be a valuable screening approach in cases characterized by prevalent founder mutations. METHODS: We screened 275 North American patients with recessive/isolate retinitis pigmentosa for two mutations: an Alu insertion in the MAK gene and the p.Lys42Glu missense in the DHDDS gene. All patients were unrelated; 35 reported Jewish ancestry and the remainder reported mixed ethnicity. RESULTS: We identified the MAK and DHDDS mutations homozygously in only 2.1% and 0.8%, respectively, of patients of mixed ethnicity, but in 25.7% and 8.6%, respectively, of cases reporting Jewish ancestry. Haplotype analyses revealed that inheritance of the MAK mutation was attributable to a founder effect. CONCLUSION: In contrast to most mutations associated with retinitis pigmentosa-which are, in general, extremely rare-the two alleles investigated here cause disease in approximately one-third of North American patients reporting Jewish ancestry. Therefore, their screening constitutes an alternative procedure to large-scale tests for patients belonging to this ethnic group, especially in time-sensitive situations.Genet Med 17 4, 285-290.

%B Genet Med %V 17 %P 285-90 %8 2015 Apr %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/25255364?dopt=Abstract %R 10.1038/gim.2014.132