Genetic characteristics and epidemiology of inherited retinal degeneration in Taiwan

Abstract

Inherited retinal degenerations (IRDs) are a group of phenotypically and genotypically heterogeneous disorders with substantial socioeconomic impact. In this cohort study, we tried to address the genetic characteristics and epidemiology of IRDs in Taiwan. Totally, 312 families with IRDs were identified and recruited and genetic testing was performed via probe capture-based NGS targeting 212 IRD-related genes. Statistical analysis was based on the proband of each affected family. Disease-causing genotypes were identified in 178 families (57.1%). ABCA4 variants were the most common cause of disease in this cohort (27 families, 15.2%), whereas CYP4V2 variants were the most common cause for the single phenotype-Bietti's crystalline dystrophy (12 families, 3.8%). Some variants such as ABCA4:c.1804C>T, CYP4V2:c.802-8_810delinsGC, and EYS:c6416G>A were population-specific disease-causing hotspots. Probands affected by ABCA4, RPGR, RP1L1, and CEP290 sought medical help earlier while patients affected by EYS and CYP4V2 visited our clinic at an older age. To evaluate the representativeness of our cohort in the genetic epidemiology of IRDs in Taiwan, our demographic data were compared with that of the total IRD population in Taiwan, obtained from the National Health Insurance Research Database. This is currently the largest-scale, comprehensive study investigating the genetic characteristics and epidemiology of IRD in Taiwan. These data could help patients and caregivers to adopt precision genomic medicine and novel gene therapies in near future.

Fig. 1. The age at examination and at onset of IRD probands by phenotype.

a The age at examination of all probands or of probands with a positive/negative family history. b The onset age of all probands or of probands with a positive/negative family. Means with different symbols are statistically significant compared to all probands by Fisher’s LSD test (***p < 0.001; **p < 0.01; *p < 0.05). FH family history.

Fig. 2. Classification of the inheritance patterns of probands with a positive/negative family history.

FH family history, AR autosomal recessive inheritance, AD autosomal dominant inheritance, XL X-linked inheritance.

Fig. 3. Number of probands grouped by disease-causing gene, phenotype, and the percentage of disease-causing gene in the probands in our cohort shown by a hollow circle.

a Number of probands by disease-causing gene and phenotype, and the percentage of disease-causing genes in 312 probands. Only the disease-causing genes in two or more probands are shown. b Number of probands by disease-causing gene and phenotype and the percentage of disease-causing genes in probands with a positive family history. c Number of probands by disease-causing gene and the phenotype and percentage of disease-causing genes in probands with a negative family history. FH family history, RP retinitis pigmentosa, MD macular dystrophy, LCA Leber congenital amaurosis, CRD cone-rod dystrophy, RS retinoschisis, CD cone dystrophy, BCD Bietti’s crystalline dystrophy, OMD occult macular dystrophy, VIRC vitreoretinochoroidopathy.

Fig. 4. The age at examination and age at onset of IRD probands grouped by the disease-causing gene.

a The age at examination of all probands. b The onset age of all probands. Mean with different symbols are statistically significant compared to all probands by Fisher’s LSD test (**p < 0.01; *p < 0.05).

Fig. 5. Age distribution of TIP and Taiwan population.

Age distribution of our cohort (TIP) and the Taiwan IRD population based on the National Health Insurance Research Database (NHIRD) of Taiwan.