Genotypic profile and phenotype correlations of ABCA4-associated retinopathy in Koreans

This study was conducted to analyze the clinical features associated with the pathogenic variants of ABCA4 in Korean patients with inherited retinal dystrophies (IRDs).

We enrolled patients with IRDs who visited a tertiary referral hospital and identified the pathogenic variants of ABCA4 through targeted gene panel sequencing and whole exome sequencing. We analyzed the clinical characteristics and phenotypic spectrum according to genotype.

Eleven patients (from nine families) with IRDs and pathogenic variants in ABCA4 were included. Eight patients (from seven families) with Stargardt disease (STGD), two (from one family) with cone-rod dystrophy (CRD), and one with early-onset retinitis pigmentosa (RP) were included. Two heterozygous mutations were identified in eight families, and one variant was found in a patient with fundus flavimaculatus. Two variants, p.Gln294Ter and p.Gln636Lys, were associated with severe phenotypes, such as early-onset RP and CRD. Four novel pathogenic variants, p.Gln636Lys, p.Ile1114del, p.Thr1117Ala, and p.Asn1588Tyr, were identified. p.Gln294Ter, p.Leu1157Ter, and p.Lys2049ArgfsTer12 were repeatedly detected in Koreans with ABCA4-associated retinal diseases (ABCA4-RD).

Various pathogenic variants of ABCA4, including four novel variants, were identified, and ABCA4-RD exhibited various phenotypes and disease severities in a Korean IRD cohort. These findings will be useful for understanding the clinical features of ABCA4-RD and ethnicity-specific variants in East Asians.