Inherited retinal degeneration in Malay and Indian populations of Singapore and Malaysia: a prospective multicentre study

To analyze the phenotypic and genotypic characteristics of inherited retinal degeneration (IRD) patients of Malay and Indian ethnicity from Singapore and Malaysia. Ethnic Malay and Indian IRD patients were consecutively enrolled from retina clinics in Singapore and Malaysia. Phenotypic and genetic data were reviewed. A total of 100 unrelated individuals (Malay: n = 46, Indian: n = 54) were enrolled. Sixteen distinct IRD phenotypes were identified, with nonsyndromic retinitis pigmentosa (RP) comprising 46% of all cases. Stargardt disease and cone-rod dystrophy accounted for 20% and 11% of cases, respectively. Exome sequencing yielded genotypes in 64.3% of Malay and 68.9% of Indian cases. Variants in ABCA4 were the most common cause of IRD overall. Recurrent variants were identified in ABCA4, GUCY2D, PRPH2, and TULP1 for Malays, and in ABCA4 and MFSD8 (CLN7) for Indians. Homozygosity was more frequent among Indians than Malays (58.1% vs. 19.2%; p = 0.003). This study demonstrated diverse phenotypic and genotypic outcomes in Malay and Indian populations of Singapore and Malaysia, with distinct differences between them. Homozygosity was common among ethnic Indian IRD cases, explaining phenotypic diversity. These findings inform the identification of regionally relevant IRDs for developing targeted therapies in Malay and Indian patients from Southeast Asia.