A single-base substitution within an intronic repetitive element causes dominant retinitis pigmentosa with reduced penetrance.

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Serval ID
serval:BIB_83091C4D4EF3
Type
Article: article from journal or magazin.
Collection
Publications
Title
A single-base substitution within an intronic repetitive element causes dominant retinitis pigmentosa with reduced penetrance.
Journal
Human Mutation
Author(s)
Frio T.R., McGee T.L., Wade N.M., Iseli C., Beckmann J.S., Berson E.L., Rivolta C.
ISSN
1098-1004[electronic]
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
30
Number
9
Pages
1340-1347
Language
english
Abstract
We report the study of a large American family displaying autosomal dominant retinitis pigmentosa with reduced penetrance, a form of hereditary retinal degeneration. Although the inheritance pattern and previous linkage mapping pointed to the involvement of the PRPF31 gene, extensive screening of all its exons and their boundaries failed in the past to reveal any mutation. In this work, we sequenced the entire PRPF31 genomic region by both the classical Sanger method and ultrahigh throughput (UHT) sequencing. Among the many variants identified, a single-base substitution (c.1374+654C>G) located deep within intron 13 and inside a repetitive DNA element was common to all patients and obligate asymptomatic carriers. This change created a new splice donor site leading to the synthesis of two mutant PRPF31 isoforms, degraded by nonsense-mediated mRNA decay. As a consequence, amounts of PRPF31 mRNA derived from the mutant allele were very reduced, with no evidence of mutant proteins being synthesized. Our results indicate that c.1374+654C>G causes retinitis pigmentosa via haploinsufficiency, similar to the vast majority of PRPF31 mutations described so far. We discuss the potential of UHT sequencing technologies in mutation screening and the continued identification of pathogenic splicing mutations buried deep within intronic regions.
Pubmed
Web of science
Create date
08/10/2009 14:26
Last modification date
20/08/2019 15:43
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