A 112 kb Deletion in Chromosome 19q13.42 Leads to Retinitis Pigmentosa

PURPOSE. This study sets out to identify novel mutations in PRPF31 in a cohort of autosomal dominant retinitis pigmentosa (adRP) patients with a history of nonpenetrance in the family. METHODS. Twenty-one patients with history of nonpenetrant autosomal dominant retinitis pigmentosa were selected; all underwent full ophthalmic examination. Multiplex ligation-dependent probe analysis (MLPA) was performed and, where a deletion was found, further family members were recruited. An individual suspected to harbor a large deletion was used as a positive control. Analysis of single nucleotide polymorphisms in the upstream region was used to determine the extent of the deletion, and the breakpoint was then characterized by PCR and sequencing. RESULTS. In one family, multiplex ligation-dependent probe analysis revealed a novel large deletion in 19q13.4 encompassing exons 1 to 13 of the PRPF31 gene. The mutation was characterized as a deletion of 112 kilobase (kb), encompassing over 90% of PRPF31 and five upstream genes: TFPT, OSCAR, NDUFA3, TARM-1, and VSTM-1. The breakpoint in the positive control family was also characterized. The mechanism of deletion in both families was Alu-mediated nonallelic homologous recombination. CONCLUSIONS. This study describes two large deletions, one in a previously reported family and one in a new family: the latter represents the largest deletion yet described on chromosome 19 and the first report of the involvement of VSTM-1. Remarkably, heterozygous deletion of this large region (encompassing six genes) produces little or no other clinical disease besides retinitis pigmentosa. (Invest Ophthalmol Vis Sci. 2011; 52: 6597-6603) DOI: 10.1167/iovs.11-7861