A novel PRPF31 splice-site mutation in a Chinese family withautosomal dominant retinitis pigmentosa

[摘要] Purpose: The autosomal dominant form of retinitis pigmentosa (ADRP)can be caused by mutations in 13 genes and a further locus for which thegene remains to be identified. This study was intended to identifymutations in a large Chinese pedigree with ADRP.Methods: A genome scan was conducted in the family. The whole codingsequences and the intron-exon boundaries of candidate genes wereamplified and sequenced. The reverse transcriptase polymerase chainreaction (RT-PCR) was performed to amplify the mutated mRNA.Results: The strongest evidence of linkage was detected with threeadjacent microsatellite markers genotyped between D19S902 and D19S210 onchromosome 19q13.33-13.43. Within the region, a single nucleotide change(G>A) at position -1 of Intron 5 of PRPF31 was found. Theconsensus AG doublet of the Intron 5 splice acceptor was changed to AA.The mutation co-segregated with the disease phenotype, suggesting thatit was the disease-causing mutation in this family. This splicing sitemutation is predicted to cause an erroneous splicing of Exon 6. ByRT-PCR, we found the mutated nucleotide of Intron 5 (A) and the firstnucleotide 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) atthe mRNA level. This change led to a frameshift and truncated protein of196 amino acids with 56 novel amino acids prior to a premature stop.Conclusions: A novel splicing mutation (IVS5-1G>A) in thepre-mRNA splicing-factor gene PRPF31 causes retinitis pigmentosa ina large Chinese family. The mutation results in a truncated protein ofPRPF31.

[学科分类] 生物化学/生物物理