J Genet Med.  2015 Dec;12(2):109-117. 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

• Hong HD
• Kim E
• Nam SH
• Yoo DH
• Suh BC
• Choi BO
• Chung KW

• KMID: 2149854
• DOI: http://doi.org/10.5734/JGM.2015.12.2.109

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.

Keyword

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

MeSH Terms

Classification
Diagnosis
DNA, Mitochondrial
Humans
Leigh Disease*
MERRF Syndrome*
Mitochondrial Diseases
Phenotype
DNA, Mitochondrial