title: Novel mutations in XLRS1 causing retinoschisis, including first evidence of putative leader sequence change.
abstract: Juvenile retinoschisis is an X-linked recessive disease caused by mutations in the XLRS1 gene. We screened 31 new unrelated patients and families for XLRS1 mutations in addition to previously reported mutations for 60 of our families (Retinoschisis Consortium, Hum Mol Genet 1998;7:1185-1192). Twenty-three different mutations including 12 novel ones were identified in 28 patients. Mutations identified in this study include 19 missense mutations, two nonsense mutations, one intragenic deletion, four microdeletions, one insertion, and one intronic sequence substitution that is likely to result in a splice site defect. Two novel mutations, c.38T-->C (L13P) and c.667T-->C (C223R), respectively, present the first genetic evidence for the functional significance of the putative leader peptide sequence and for the functional significance at the carboxyl terminal of the XLRS1 protein beyond the discoidin domain. Mutations in 25 of the families were localized to exons 4-6, emphasizing the critical functional significance of the discoidin domain of the XLRS1 protein.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor 48105, USA. khiri@umich.edu
authors.forename: K T
authors.initials: KT
authors.lastname: Hiriyanna
authors.forename: E L
authors.initials: EL
authors.lastname: Bingham
authors.forename: B M
authors.initials: BM
authors.lastname: Yashar
authors.forename: R
authors.initials: R
authors.lastname: Ayyagari
authors.forename: G
authors.initials: G
authors.lastname: Fishman
authors.forename: K W
authors.initials: KW
authors.lastname: Small
authors.forename: D V
authors.initials: DV
authors.lastname: Weinberg
authors.forename: R G
authors.initials: RG
authors.lastname: Weleber
authors.forename: R A
authors.initials: RA
authors.lastname: Lewis
authors.forename: S
authors.initials: S
authors.lastname: Andreasson
authors.forename: J E
authors.initials: JE
authors.lastname: Richards
authors.forename: P A
authors.initials: PA
authors.lastname: Sieving
mesh_terms: D002648:Child; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D017354:Point Mutation; D021382:Protein Sorting Signals / Q000235:genetics; D012162:Retinal Degeneration / Q000235:genetics*; D017384:Sequence Deletion; D014960:X Chromosome / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D005136:Eye Proteins; D021382:Protein Sorting Signals; C108726:RS1 protein, human