title: Four USH2A founder mutations underlie the majority of Usher syndrome type 2 cases among non-Ashkenazi Jews.
abstract: Type 2 Usher syndrome (USH2) is a recessively inherited disorder, characterized by the combination of early onset, moderate-to-severe, sensorineural hearing loss, and vision impairment due to retinitis pigmentosa. From 74% to 90% of USH2 cases are caused by mutations of the USH2A gene. USH2A is composed of 72 exons, encoding for usherin, an extracellular matrix protein, which plays an important role in the development and maintenance of neurosensory cells in both retina and cochlea. To date, over 70 pathogenic mutations of USH2A have been reported in individuals of various ethnicities. Many of these mutations are rare private mutations segregating in single families. The aim of the current work was to investigate the genetic basis for USH2 among Jews of various origins. We found that four USH2A mutations (c.239-240insGTAC, c.1000C>T, c.2209C>T, and c.12067-2A>G) account for 64% of mutant alleles underlying USH2 in Jewish families of non-Ashkenazi descent. Considering the very large size of the USH2A gene and the high number of mutations detected in USH2 patients worldwide, our findings have significant implications for genetic counseling and carrier screening in various Jewish populations.
authors.affiliation: Department of Genetics and The Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Auslender
authors.forename: Dikla
authors.initials: D
authors.lastname: Bandah
authors.forename: Leah
authors.initials: L
authors.lastname: Rizel
authors.forename: Doron M
authors.initials: DM
authors.lastname: Behar
authors.forename: Mordechai
authors.initials: M
authors.lastname: Shohat
authors.forename: Eyal
authors.initials: E
authors.lastname: Banin
authors.forename: Stavit
authors.initials: S
authors.lastname: Allon-Shalev
authors.forename: Reuven
authors.initials: R
authors.lastname: Sharony
authors.forename: Dror
authors.initials: D
authors.lastname: Sharon
authors.forename: Tamar
authors.initials: T
authors.lastname: Ben-Yosef
mesh_terms: D000352:Africa, Northern; D000595:Amino Acid Sequence; D000818:Animals; D004285:Dogs; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics*; D018703:Founder Effect; D006239:Haplotypes; D006801:Humans; D007585:Jews / Q000208:ethnology* / Q000235:genetics*; D051379:Mice; D008877:Middle East; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D051381:Rats; D052245:Usher Syndromes / Q000235:genetics* / Q000503:physiopathology
chemical_list: D016326:Extracellular Matrix Proteins; C112735:USH2A protein, human