title: A novel missense SNRNP200 mutation associated with autosomal dominant retinitis pigmentosa in a Chinese family.
abstract: The SNRNP200 gene encodes hBrr2, a helicase essential for pre-mRNA splicing. Six mutations in SNRNP200 have recently been discovered to be associated with autosomal dominant retinitis pigmentosa (adRP). In this work, we analyzed a Chinese family with adRP and identified a novel missense mutation in SNRNP200. To identify the genetic defect in this family, exome of the proband was captured and sequencing analysis was performed to exclude known genetic defects and find possible pathogenic mutations. Subsequently, candidate mutations were validated in affected family members using Sanger sequencing. A novel missense mutation, c.2653C>G transition (p.Q885E), in exon 20 of SNRNP200 was identified. The mutation co-segregated with the disease phenotype over four generations and was absent in 100 normal unaffected individuals. This mutation occurs at highly conserved position in hBrr2 and is predicted to have a functional impact, suggesting that hBrr2-dependent small nuclear riboproteins (snRNPs) unwinding and spliceosome activation is important in the pathogenesis of some variants of RP.
authors.affiliation: Department of Ophthalmology, Chinese PLA General Hospital, Beijing, China. ltc301@yahoo.com.cn
authors.forename: Tiecheng
authors.initials: T
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.forename: Xuemin
authors.initials: X
authors.lastname: Zhang
authors.forename: Huijun
authors.initials: H
authors.lastname: Yuan
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.forename: Janet
authors.initials: J
authors.lastname: Lee
authors.forename: Baoquan
authors.initials: B
authors.lastname: Zhang
authors.forename: Maonian
authors.initials: M
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.forename: Geng
authors.initials: G
authors.lastname: Tian
authors.forename: Weifeng
authors.initials: W
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002681:China; D005091:Exons; D005190:Family; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D019721:Ophthalmoscopes; D010375:Pedigree; D011487:Protein Conformation; D012174:Retinitis Pigmentosa / Q000235:genetics*; D017411:Ribonucleoproteins, Small Nuclear / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D055815:Young Adult
chemical_list: D017411:Ribonucleoproteins, Small Nuclear; C545711:SNRNP200 protein, human