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Human Molecular Genetics, 2002, Vol. 11, No. 1 87-92
© 2002 Oxford University Press

Mutations in HPRP3, a third member of pre-mRNA splicing factor genes, implicated in autosomal dominant retinitis pigmentosa

Christina F. Chakarova1, Matthew M. Hims2, Hanno Bolz3, Leen Abu-Safieh1, Reshma J. Patel1, Myrto G. Papaioannou1, Chris F. Inglehearn2, T. Jeffrey Keen2, Catherine Willis4, Anthony T. Moore1,4, Thomas Rosenberg5, Andrew R. Webster1,4, Alan C. Bird1,4, Andreas Gal3, David Hunt1, Eranga N. Vithana1,+ and Shomi S. Bhattacharya1

1Department of Molecular Genetics, Institute of Ophthalmology, University College London, 11–43 Bath Street, London EC1V 9EV, UK, 2Molecular Medicine Unit, University of Leeds, Clinical Science Building, St James’ University Hospital, Leeds LS9 7TF, UK, 3Institute of Human Genetics, University Hospital Eppendorf, Butenfeld 32, D-22529 Hamburg, Germany, 4Moorfields Eye Hospital, London EC1V 2PD, UK and 5National Eye Clinic for the Visually Impaired, Hellerup, Denmark

Retinitis pigmentosa (RP), the commonest form of inherited retinal dystrophies is a clinically and genetically heterogeneous disorder. It is characterized by progressive degeneration of the peripheral retina leading to night blindness and loss of peripheral visual field. RP is inherited either in an autosomal dominant, autosomal recessive or X-linked mode. A locus (RP18) for autosomal dominant RP was previously mapped by linkage analysis in two large pedigrees to chromosome 1p13–q21. The human HPRP3 gene, the orthologue of the yeast pre-mRNA splicing factor (PRP3), localizes within the RP18 disease interval. The recent identification of mutations in human splicing factors, PRPF31 and PRPC8, led us to screen HPRP3 as a candidate in three chromosome 1q-linked families. So far, two different missense mutations in two English, a Danish family and in three RP individuals have been identified. Both mutations are clustered within a two-codon stretch in the 11th exon of the HPRP3 gene. Interestingly, one of the mutations (T494M) is seen repeatedly in apparently unlinked families raising the possibility of a mutation hot spot. This has been confirmed by haplotype analysis using SNPs spanning the HPRP3 gene region supporting multiple origins of the mutation. The altered HPRP3 amino acids, which are highly conserved in all known HPRP3 orthologues, indicate a major function of that domain in the splicing process. The identification of mutations in a third pre-mRNA splicing factor gene further highlights a novel mechanism of photoreceptor degeneration due to defects in the splicing process.

+ To whom correspondence should be addressed. Tel: +44 20 76086920; Fax: +44 20 76086863; Email: evithana@hgmp.mrc.ac.ukThe authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors


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[Abstract] [Full Text] [PDF]

Home page
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