Prognosis for splicing factor PRPF8 retinitis pigmentosa, novel mutations and correlation between human and yeast phenotypes
| Autor: | Rajarshi Mukhopadhyay, Graeme C.M. Black, James O'Sullivan, Cécilia Maubaret, Athina Kipioti, Chris F. Inglehearn, Vernon Long, Martin McKibbin, Raj Ramesar, Anthony T. Moore, Parastoo Ehsani, Andrew R. Webster, Katherine V. Towns, Kelly Springell, Jean D. Beggs, Mohammed Kamal, Veronika Vaclavik, Shomi S. Bhattacharya, David A. Mackey, Eric A. Pierce |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Spliceosome Adolescent Mutation Missense RNA-binding protein Biology Bioinformatics Young Adult Exon Splicing factor Yeasts Retinitis pigmentosa Genetics medicine Humans Missense mutation Genetics(clinical) Child Genetics (clinical) Aged RNA-Binding Proteins Middle Aged Prognosis medicine.disease Phenotype Child Preschool Mutation RNA splicing Female Carrier Proteins Retinitis Pigmentosa |
| Zdroj: | 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 M, O'Sullivan, J, Bhattacharya, S S, Pierce, E A, Beggs, J D & Inglehearn, C F 2010, ' Prognosis for Splicing Factor PRPF8 Retinitis Pigmentosa, Novel Mutations and Correlation between Human and Yeast Phenotypes ', Human Mutation, vol. 31, no. 5, pp. E1361-E1376 . https://doi.org/10.1002/humu.21236 |
| ISSN: | 1098-1004 1059-7794 |
| DOI: | 10.1002/humu.21236 |
| Popis: | 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. (C) 2010 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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