Genetic detection of a novel pathogenic variant in patients with early-onset severe retinal dystrophy.

Purpose: Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) are genetic disorders affecting the retina, causing significant visual impairment from early childhood. Although over 26 genes have been implicated in EOSRD, the genetic basis remains incompletely characterized in a subset of cases. Our study aims to understand the mutational spectrum of LRAT-related EOSRD in an autosomal recessive family.

Methods: Patients underwent comprehensive eye exams with ultra-widefield fundus photography, optical coherence tomography, and fundus autofluorescence. Whole-exome sequencing screened patients and parents, with results confirmed by Sanger sequencing co-segregation analysis. Conservation and in-silico analyses assessed the pathogenicity of the variant and its effect on the encoded protein.

Results: A Chinese family with two patients and two carriers participated in this study. A novel homozygous LRAT (NM_004744.5) missense mutation (c.578 G>T, p.Arg193Ile) was identified and confirmed by segregation analysis. Predictive tools suggested that this mutation was harmful, and p.Arg193Ile was located in a highly conserved region of the LRAT protein, indicating potential detrimental effects on protein function.

Conclusions: A novel homozygous missense mutation in LRAT (NM_004744.5):c.578 G>T (p.Arg193Ile) was identified in this Han Chinese family with early-onset severe retinal dystrophy. Our research identified a connection between variations in the LART gene and EOSRD, suggesting that further studies are needed to understand the underlying causes of this disease. This discovery expands the mutation spectrum in LRAT and offers valuable insights for exploring the molecular mechanisms involved in the development of EOSRD.