title: Two specific mutations are prevalent causes of recessive retinitis pigmentosa in North American patients of Jewish ancestry.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Giulia
authors.initials: G
authors.lastname: Venturini
authors.affiliation: Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Koskiniemi-Kuendig
authors.affiliation: The Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
authors.forename: Shyana
authors.initials: S
authors.lastname: Harper
authors.affiliation: The Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
authors.forename: Eliot L
authors.initials: EL
authors.lastname: Berson
authors.affiliation: Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Carlo
authors.initials: C
authors.lastname: Rivolta
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000235:genetics*; D000483:Alleles; D020087:Alu Elements / Q000235:genetics; D000595:Amino Acid Sequence; D005091:Exons; D005808:Genes, Recessive; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007585:Jews; D020125:Mutation, Missense; D009656:North America; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology; D014481:United States
chemical_list: D019883:Alkyl and Aryl Transferases; C051389:dehydrodolichyl diphosphate synthetase; D017346:Protein Serine-Threonine Kinases; C081931:MAK protein, human