Prognosis for splicing factor PRPF8 retinitis pigmentosa, novel mutations and correlation between human and yeast phenotypes.
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.
Section of Ophthalmology and Neuroscience, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK.
Katherine V
KV
Towns
Athina
A
Kipioti
Vernon
V
Long
Martin
M
McKibbin
Cecilia
C
Maubaret
Veronika
V
Vaclavik
Parastoo
P
Ehsani
Kelly
K
Springell
Mohammed
M
Kamal
Raj S
RS
Ramesar
David A
DA
Mackey
Anthony T
AT
Moore
Rajarshi
R
Mukhopadhyay
Andrew R
AR
Webster
Graeme C M
GC
Black
James
J
O'Sullivan
Shomi S
SS
Bhattacharya
Eric A
EA
Pierce
Jean D
JD
Beggs
Chris F
CF
Inglehearn
D000293:Adolescent; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D011379:Prognosis; D016601:RNA-Binding Proteins; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology; D015003:Yeasts / Q000235:genetics*; D055815:Young Adult
D002352:Carrier Proteins; C115374:PRPF8 protein, human; D016601:RNA-Binding Proteins