Autosomal dominant retinitis pigmentosa with macular involvement associated with a disease haplotype that included a novel <italic>PRPH2</italic> variant (p.Cys250Gly).

<bold>Background</bold>: It is known that <italic>PRPH2</italic> variants appear to be rare causes of retinitis pigmentosa (RP) in the Japanese population. The purpose of this study was to describe clinical and genetic features in autosomal dominant RP (adRP) patients with a novel disease-causing variant in the <italic>PRHP2</italic> gene. <bold>Materials and methods</bold>: A total of 57 unrelated Japanese probands with adRP were investigated in this study. Comprehensive ophthalmic examinations include fundus photography, fundus autofluorescence imaging, spectral-domain optical coherence tomography, and electroretinography. Whole exome sequencing or Sanger sequencing for 25 targeted exons of multiple genes causing adRP was performed to identify disease-causing variants. Co-segregation and haplotype analyses were performed to determine a disease-causing gene variant and its haplotype. <bold>Results</bold>: Genetic analysis identified a novel heterozygous <italic>PRPH2</italic> variant (c.748T>G, p.Cys250Gly) as disease causing in four probands from four families. The variant co-segregated with the RP phenotype in the eight affected patients in all families. At least three of the four families shared the same haplotype for the variant allele. Clinically, seven of the eight affected patients exhibited typical RP presentation, as well as variable macular involvement including cystoid macular change, vitelliform-like appearance, choroidal neovascularization, and macular atrophy. <bold>Conclusions</bold>: The same disease haplotype that included a novel <italic>PRPH2</italic> variant (p.Cys250Gly) was identified in three of the four Japanese families with adRP, suggesting a founder effect. Our clinical findings indicate that adRP caused by the p.Cys250Gly variant may accompany macular involvement with high frequency. [ABSTRACT FROM AUTHOR]