Confirmation of TTC8 as a disease gene for nonsyndromic autosomal recessive retinitis pigmentosa (RP51)

Abstract

Nonsyndromic retinitis pigmentosa (RP) is genetically highly heterogeneous, with >100 disease genes identified. However, mutations in these genes explain only 60% of all RP cases. Blood samples were collected from 12 members of an autosomal recessive RP family. Whole genome homozygosity mapping and haplotype analysis placed the RP locus in this family at chromosome 14q31.3. Whole-exome sequencing (WES) in proband revealed a mutation in TTC8, which was flagged as most likely candidate gene by bioinformatic analysis. TTC8 is mutated in Bardet-Biedl syndrome 8 (BBS8), and once reported previously in a family with nonsyndromic RP. Sequencing of amplified products of exon 13 of TTC8 validated c.1347G>C (p.Gln449His), a novel change that affects the final nucleotide of exon 13 and might deleteriously affect splicing. This mutation segregated completely with the disease in the family and was not observed in 100 ethnically matched controls from same population. This represents second report of a TTC8 mutation in nonsyndromic RP, thus confirming the identity of TTC8 as causative gene for RP51.

Keywords: TTC8/RP51 locus; haplotype analysis; nonsyndromic arRP with macular degeneration; whole-exome sequencing; whole-genome homozygosity mapping.