Genetic characteristics of retinitis pigmentosa in 1204 Japanese patients.

Abstract

The genetic profile of retinitis pigmentosa (RP) in East Asian populations has not been well characterised. Therefore, we conducted a large-scale sequencing study to investigate the genes and variants causing RP in a Japanese population. A total of 1209 Japanese patients diagnosed with typical RP were enrolled. We performed deep resequencing of 83 known causative genes of RP using next-generation sequencing. We defined pathogenic variants as those that were putatively deleterious or registered as pathogenic in the Human Gene Mutation Database or ClinVar database and had a minor allele frequency in any ethnic population of ≤0.5% for recessive genes or ≤0.01% for dominant genes as determined using population-based databases. We successfully sequenced 1204 patients with RP and determined 200 pathogenic variants in 38 genes as the cause of RP in 356 patients (29.6%). Variants in six genes (<i>EYS</i>, <i>USH2A</i>, <i>RP1L1</i>, <i>RHO</i>, <i>RP1</i> and <i>RPGR</i>) caused RP in 65.4% (233/356) of those patients. Among autosomal recessive genes, two known founder variants in <i>EYS</i> [p.(Ser1653fs) and p.(Tyr2935*)] and four East Asian-specific variants [p.(Gly2752Arg) in <i>USH2A</i>, p.(Arg658*) in <i>RP1L1</i>, p.(Gly2186Glu) in <i>EYS</i> and p.(Ile535Asn) in <i>PDE6B</i>] and p.(Cys934Trp) in <i>USH2A</i> were found in ≥10 patients. Among autosomal dominant genes, four pathogenic variants [p.(Pro347Leu) in <i>RHO</i>, p.(Arg872fs) in <i>RP1</i>, p.(Arg41Trp) in <i>CRX</i> and p.(Gly381fs) in <i>PRPF31</i>] were found in ≥4 patients, while these variants were unreported or extremely rare in both East Asian and non-East Asian population-based databases. East Asian-specific variants in causative genes were the major causes of RP in the Japanese population.