[P1-204] Consecutive analysis of Leigh syndrome in Korea: clinical and genetic spectrum
Leigh syndrome (LS) is one of the most common mitochondrial disorders, which is characterized by various neurodegenerative features and bilateral symmetric central nervous system lesions. To date, mutations in more than 75 genes have been identified in both mitochondrial and nuclear genome. The aim of this study was to discover the causative nuclear genes in LS by using whole exome sequencing. We included 35 patients with LS at the Seoul National University Children’s Hospital from 2001 to 2015. Diagnosis was based on characteristic clinical, biochemical features and radiologic findings. We excluded the patients with mtDNA mutations. Pathogenic variants in various genes previously shown to cause LS were identified in 14 patients (14/34=41.2%): NDUFS1 (1), NDUFV1 (1), NDUFAF6 (2), SURF1 (2), SLC19A3 (2), ECHS1 (2), PNPT1 (1), IARS2 (2), and NARS2 (1). All except 3 of the pathogenic variants have never been reported. Of note, mutations in genes associated with mitochondrial translation were frequently observed (4/14=28.6%). Additionally there were two novel candidate genes identified in 3 patients (3/34=8.8%), of which the functions have not been discovered in human: APOA1BP (1) and VPS13D (2). There was poor genotype-phenotype correlation with literature review. Our findings suggest that LS has a genetic heterogeneity, showing mutations in mitochondrial translation and valine metabolism as well as oxidative phosphorylation system or assembly factors. Also, we re-validate the clinical utility of whole exome sequencing in identifying causative genes in patients with LS. Discovery of molecular defects in Korean LS might prompt us to develop the gene panel.