Mutation spectrum and genotype-phenotype correlation of inherited retinal dystrophy in Taiwan

Inherited retinal dystrophy (IRD) is a group of irreversible retinal degenerative disorders with significant genotypic and phenotypic heterogeneity, which cause difficulty in making a precise clinical diagnosis. Furthermore, the mutation spectrum of IRD in Taiwan remains unknown. Therefore, our study focused on investigating the spectrum of mutations among Taiwanese families with IRD using targeted exome sequencing (TES) technology.

We recruited a total of 60 unrelated Taiwanese families with IRD; most of them were retinitis pigmentosa. We employed TES to investigate 284 candidate genes. Bioinformatics analysis, Sanger sequencing-based co-segregation testing, and computational assessment were performed to validate each mutation and its pathogenicity. The genotype-phenotype correlation was analysed in all patients with mutations defined in the guidelines provided by the American College of Medical Genetics.

We successfully identified genetic causes in 32 families (detection rate of 53.3%). Among them, 16 had a sporadic inheritance (16/36, 44.4%); eight had an autosomal recessive inheritance (8/14, 57.1%); four had an autosomal dominant inheritance (4/5, 80%); four had an X-linked inheritance (4/5, 80%). Among 38 pathological mutations in 19 known genes, 20 mutations are reported here for the first time. Novel mutation spectrum and genotype-phenotype correlations were revealed as well.

Here we achieved a detection rate of 53.3% and elucidated the mutation spectrum in Taiwanese families with IRD for the first time. The results indicated that CYP4V2 and USH2A might be the most common pathogenic genes in IRD patients in Taiwan.