title: A novel PRPF31 splice-site mutation in a Chinese family with autosomal dominant retinitis pigmentosa.
abstract: OBJECTIVE
  The autosomal dominant form of retinitis pigmentosa (ADRP) can be caused by mutations in 13 genes and a further locus for which the gene remains to be identified. This study was intended to identify mutations in a large Chinese pedigree with ADRP.
  
  
  METHODS
  A genome scan was conducted in the family. The whole coding sequences and the intron-exon boundaries of candidate genes were amplified and sequenced. The reverse transcriptase polymerase chain reaction (RT-PCR) was performed to amplify the mutated mRNA.
  
  
  RESULTS
  The strongest evidence of linkage was detected with three adjacent microsatellite markers genotyped between D19S902 and D19S210 on chromosome 19q13.33-13.43. Within the region, a single nucleotide change (G>A) at position -1 of Intron 5 of PRPF31 was found. The consensus AG doublet of the Intron 5 splice acceptor was changed to AA. The mutation co-segregated with the disease phenotype, suggesting that it was the disease-causing mutation in this family. This splicing site mutation is predicted to cause an erroneous splicing of Exon 6. By RT-PCR, we found the mutated nucleotide of Intron 5 (A) and the first nucleotide of Exon 6 (G) was regarded as a new splice acceptor, resulting in 1 bp deletion of the first codon of Exon 6 (GAG-to-AG) at the mRNA level. This change led to a frameshift and truncated protein of 196 amino acids with 56 novel amino acids prior to a premature stop.
  
  
  CONCLUSIONS
  A novel splicing mutation (IVS5-1G>A) in the pre-mRNA splicing-factor gene PRPF31 causes retinitis pigmentosa in a large Chinese family. The mutation results in a truncated protein of PRPF31.
authors.affiliation: National Laboratory of Medical Genetics of China, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China. nlmglcy@xysm.net
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.forename: Duo
authors.initials: D
authors.lastname: Zheng
authors.forename: Qian
authors.initials: Q
authors.lastname: Pan
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Xinghua
authors.initials: X
authors.lastname: Xi
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Hu
authors.forename: Hao
authors.initials: H
authors.lastname: Deng
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.forename: Deyong
authors.initials: D
authors.lastname: Jiang
authors.forename: Hanxiang
authors.initials: H
authors.lastname: Deng
authors.forename: Jiahui
authors.initials: J
authors.lastname: Xia
mesh_terms: D044466:Asian People / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D010375:Pedigree; D022821:RNA Splice Sites / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005136:Eye Proteins; C454222:PRPF31 protein, human; D022821:RNA Splice Sites; D012333:RNA, Messenger