Analysis of secondary mtDNA mutations in families with Leber's hereditary optic neuropathy: Four novel variants and their association with clinical presentation

Abstract

Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by subacute optic atrophy which results in severe visual impairment. The penetrance, clinical expression and disease onset are variable, and frequently associated with other extraocular symptoms. The disease phenotype remains to be an intriguing question which is dependent upon primary as well as secondary mtDNA mutations. In this study we analyzed the whole mtDNA sequence in six LHON families from Serbian population. The mtDNA sequencing was performed by Sanger's method and various bioinformatic tools were used for analysis of detected mutations. LHON patients carry all three (m.3460G > A, m.11778G > A and m.14484 T > C) primary mutations, together with numerous secondary mtDNA mutations. Four novel mutations (m.4516G > A, m.8779C > T, m.13138G > A and m.15986insG) in four different families were discovered. The m.8779C > T and m.13138G > A mutations could have a potential influence on LHON symptoms, but the issue of effect of secondary mtDNA mutations in LHON patients needs to be better clarified in future studies.

Keywords: Leber’s hereditary optic neuropathy; Mitochondria; Secondary mutation.