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S.J. Bowne, S.P. Daiger, J.R. Heckenlively, D.G. Birch, D.H. Wheaton, L.S. Sullivan; Exonic Deletions in Autosomal Dominant Retinitis Pigmentosa Genes May Be a Frequent Cause of Retinal Disease . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1705.
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© ARVO (1962-2015); The Authors (2016-present)
Screening the known autosomal dominant retinitis pigmentosa genes by DNA sequencing results in the identification of a disease–causing mutation in only 50% of families. The cause of disease in the remaining 50% is unknown and may be either due to mutations in additional genes or due to mutations in the known genes that are undetectable by sequencing. We are using a recently developed technique called MLPA (Multiplex Ligation–dependent Probe Amplification) to screen several adRP genes for exonic deletions.
MLPA is being used to screen 95 probands for deletions in PRPF31, rhodopsin, RP1 and RPE65. These probands have tested negative for mutations in the known adRP genes by sequencing. MLPA probes for rhodopsin, RP1 and RPE65 were designed and produced by MRC–Holland in kit form while probes for PRPF31 were developed by our laboratory.
Two of the first 20 samples tested by MLPA showed evidence of an exonic deletion in the PRPF31 gene. One family has an apparent deletion of exons 4–12 which segregates with disease in five affected family members. The second family appears to have a deletion encompassing the entire PRPF31 gene. Work is ongoing to determine the deletion breakpoints and to complete the screening of the remaining 75 families.
Preliminary results suggest that large deletions may be a frequent cause of the RP11 form of adRP. Additional analysis of PRPF31 and other adRP genes by MLPA will determine if exonic deletions, not detectible by conventional methods, account for a substantial fraction of the currently unidentified adRP mutations.
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