Abstract
Purpose :
To identify mutational spectrum of Leber congenital amaurosis (LCA) in 43 unrelated Korean patients
Methods :
A retrospective case series was conducted in 43 unrelated, consecutive patients with LCA who underwent genetic testing between June 1, 2015 and October 31, 2018. Next-generation sequencing analysis was performed using a target panel that included 113 genes (n=27) or 429 gene (n=11) or whole exome sequencing (n=5). Variants were filtered and prioritized by in-depth clinical review, and finally classified according to the American College of Medical Genetics and Genomics guidelines.
Results :
All patients were of a single ethnicity (Korean). Genetic variants that were highly likely to be causative were identified in 36 of the 43 patients, corresponding to a molecular diagnostic yield of 83.7%. Among 36 patients, 9 were NMNAT1, 7 were GUCY2D, 6 were RPGRIP1, and 5 patients were CEP290. NMNAT1 c.709C>T:p.Arg237Cys variant was detected in all 9 patients, including 1 homozygous patient. The minor allele frequency of c.709C>T in NMNAT1 was higher in South Korea (MAF=0.0010, n=3818) than all population (MAF=0.0000495, n=282780) in gnome aggregation dataset.
Conclusions :
NMNAT1 is the most frequently mutated gene in patients with LCA in South Korea. On East Aisa, LCA is frequently from recessive NMNAT1 mutations, most of which are a founder c.709C>T mutation.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.