Staff Members - Benha University
Prognosis for Splicing Factor PRPF8 Retinitis Pigmentosa, Novel Mutations and Correlation between Human and Yeast Phenotypes
• 2010
Publication Information
Authors
Katherine V. Towns1*, Athina Kipioti2,3*, Vernon Long2, Martin McKibbin2, Cecilia Maubaret4, Veronika Vaclavik5, Parastoo Ehsani6, Kelly Springell1, Mohammed Kamal1, Raj S. Ramesar7, David A. Mackey8, Anthony T. Moore4, Rajarshi Mukhopadhyay4, Andrew R. W
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publication.type
International
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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. ©2010 Wiley-Liss, Inc.
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. ©2010 Wiley-Liss, Inc.