Ophthalmic Genet. 2025 Sep 24:1-6. doi: 10.1080/13816810.2025.2563909. Online ahead of print.
ABSTRACT
INTRODUCTION: We report the case of a 42-year-old Venezuelan woman with childhood-onset autosomal recessive retinitis pigmentosa type 90 (RP90), presenting an unusual and distinctive clinical phenotype characterized by macular pseudocoloboma, very early-onset acquired color vision disorder progressing to severe functional dyschromatopsia, and early-onset severe posterior subcapsular cataracts. Her affected brother exhibited a similar phenotype, while her parents and the other two siblings remained unaffected.
METHODS AND RESULTS: Massive parallel sequencing identified two novel IDH3A variants: c.127G>T (chr15:78449926 G>T; no dbSNP entry) and c.419T>C (chr15:78454052T>C; no dbSNP entry), in compound heterozygosity and confirmed to be in trans location. Both missense variants, absent from population databases, were predicted to be deleterious by multiple in silico tools and are located in critical domains involved in enzymatic complex stability, catalytic activity and subunit interactions.
CONCLUSIONS: This case reinforces the association between IDH3A mutations and RP90, corroborates key phenotypic features described in limited published reports-the presence of macular pseudocoloboma-and expands the mutational spectrum of the gene. Moreover, it highlights the role of mitochondrial metabolism in photoreceptor degeneration and proposes a link between them. Our findings underscore the need for functional studies to elucidate the pathogenic mechanisms underlying IDH3A-related retinopathies.
PMID:40993038 | DOI:10.1080/13816810.2025.2563909