Prognosis for splicing factor PRPF8 retinitis pigmentosa, novel mutations and correlation between human and yeast phenotypes.

Details

Serval ID
serval:BIB_BD9C3479E804
Type
Article: article from journal or magazin.
Collection
Publications
Title
Prognosis for splicing factor PRPF8 retinitis pigmentosa, novel mutations and correlation between human and yeast phenotypes.
Journal
Human mutation
Author(s)
Towns K.V., Kipioti A., Long V., McKibbin M., Maubaret C., Vaclavik V., Ehsani P., Springell K., Kamal M., Ramesar R.S., Mackey D.A., Moore A.T., Mukhopadhyay R., Webster A.R., Black G.C., O'Sullivan J., Bhattacharya S.S., Pierce E.A., Beggs J.D., Inglehearn C.F.
ISSN
1098-1004 (Electronic)
ISSN-L
1059-7794
Publication state
Published
Issued date
05/2010
Peer-reviewed
Oui
Volume
31
Number
5
Pages
E1361-76
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
PRPF8-retinitis pigmentosa is said to be severe but there has been no overview of phenotype across different mutations. We screened RP patients for PRPF8 mutations and identified three new missense mutations, including the first documented mutation outside exon 42 and the first de novo mutation. This brings the known RP-causing mutations in PRPF8 to nineteen. We then collated clinical data from new and published cases to determine an accurate prognosis for PRPF8-RP. Clinical data for 75 PRPF8-RP patients were compared, revealing that while the effect on peripheral retinal function is severe, patients generally retain good visual acuity in at least one eye until the fifth or sixth decade. We also noted that prognosis for PRPF8-RP differs with different mutations, with p.H2309P or p.H2309R having a worse prognosis than p.R2310K. This correlates with the observed difference in growth defect severity in yeast lines carrying the equivalent mutations, though such correlation remains tentative given the limited number of mutations for which information is available. The yeast phenotype is caused by lack of mature spliceosomes in the nucleus, leading to reduced RNA splicing function. Correlation between yeast and human phenotypes suggests that splicing factor RP may also result from an underlying splicing deficit.
Keywords
Adolescent, Adult, Aged, Carrier Proteins/genetics, Child, Child, Preschool, Female, Humans, Male, Middle Aged, Mutation, Mutation, Missense, Phenotype, Prognosis, RNA-Binding Proteins, Retinitis Pigmentosa/genetics, Retinitis Pigmentosa/pathology, Yeasts/genetics, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
20/03/2024 9:38
Last modification date
04/04/2024 15:12
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