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Mol Vis. 2004 May 20;10:361-5.

A novel PRPF31 splice-site mutation in a Chinese family with autosomal dominant retinitis pigmentosa.

Author information

1
National Laboratory of Medical Genetics of China, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China. nlmglcy@xysm.net

Abstract

PURPOSE:

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.

PMID:
15162096
[Indexed for MEDLINE]
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