Journal of Genetic Medicine  2015;12(2):109-117

doi:10.5734/JGM.2015.12.2.109

Identification of causative mutations in patients with Leigh syndrome and MERRF by mitochondrial DNA-targeted next-generation sequencing.

Hyun Dae HONG 1 ; Eunja KIM ; Soo Hyun NAM ; Da Hye YOO ; Bum Chun SUH ; Byung Ok CHOI ; Ki Wha CHUNG

Affiliations

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Keywords

Leigh disease; MERRF syndrome; Mitochondrial DNA; MT-ATP6; Mitochondrially encoded tRNA lysine gene; High-throughput nucleotide

Country

Republic of Korea

Language

English

Abstract

PURPOSE: Mitochondrial diseases are clinically and genetically heterogeneous disorders, which make their exact diagnosis and classification difficult. The purpose of this study was to identify pathogenic mitochondrial DNA (mtDNA) mutations in 2 Korean families with myoclonic epilepsy with ragged-red fibers (MERRF) and Leigh syndrome, respectively. MATERIALS AND METHODS: Whole mtDNAs were sequenced by the method of mtDNA-targeted next-generation sequencing (NGS). RESULTS: Two causative mtDNA mutations were identified from the NGS data. An m.8344A>G mutation in the tRNA-Lys gene (MT-TK ) was detected in a MERRF patient (family ID: MT132), and an m.9176T>C (p.Leu217Pro) mutation in the mitochondrial ATP6 gene (MT-ATP6) was detected in a Leigh syndrome patient (family ID: MT130). Both mutations, which have been reported several times before in affected individuals, were not found in the control samples. CONCLUSION: This study suggests that mtDNA-targeted NGS will be helpful for the molecular diagnosis of genetically heterogeneous mitochondrial diseases with complex phenotypes.