Photo Credit: Naeblys

A study of patients with inherited retinal dystrophy has identified 14 novel ABCA4 gene variants, eight of which were identified as either disease-causing or likely disease-causing. The findings from Kevin Gregory-Evans, MD, PhD, and colleagues could help reduce the need for labor-intensive in vitro and in vivo assessments of novel ABCA4 variants. Researchers evaluated 64 patients with an inherited retinal dystrophy diagnosis with ABCA4 variants. Variants of uncertain significance (VUS) were further evaluated using a cryo-electron structural model of the ABCA4 protein to predict their impact on protein function. VUS were also assessed for evolutionary conservation. The study conclusively found disease-causing biallelic ABCA4 variants in 52 patients with Stargardt’s disease, cone-rod dystrophy, macular dystrophy, or pattern dystrophy. Of a further 14 novel variants, five were reclassified as pathogenic and three as likely pathogenic, based on in silico modeling, protein modeling, and evolutionary conservation.