LCA5, a rare genetic cause of leber congenital amaurosis in Koreans.

PURPOSE: Leber congenital amaurosis (LCA), the most severe form of inherited retinal dystrophy, is a genetically heterogenous disorder and more than nine genes only account for about half of LCA cases. Recently, LCA5 was identified as a rare genetic cause of LCA. Here, we analyzed the LCA5 gene in 14 LCA patients with no mutation identified in any other known LCA genes and 3 patients with one unclassified missense variant in RPGRIP1.
METHODS: We analyzed all exons and flanking regions of the LCA5 gene using direct sequencing. We included 170 control subjects in this study to screen novel sequence variant and analyzed the functional effect of a missense variant using in-silico prediction.
RESULTS: No pathogenic mutation in LCA5 was found in our seventeen patients including 3 patients with one unclassified missense variant in RPGRIP1. We identified one novel missense variant, c.1642C>T (p.Pro548Ser), in exon 9. We considered it benign because it was found in control subjects and predicted not to be harmful to protein function on in-silico prediction. We identified another intronic variant, which has been confirmed to be benign through mRNA analysis.
CONCLUSIONS: This result shows that mutation in LCA5 is likely to be a rare genetic cause in Koreans and suggests that further investigation to identify other causative genes is necessary in Koreans.