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01-07-2010 | ORIGINAL ARTICLE

Molecular characterization of six Chinese families with m.3460G>A and Leber hereditary optic neuropathy

Authors: Dandan Yu, Xiaoyun Jia, A-Mei Zhang, Xiangming Guo, Ya-Ping Zhang, Qingjiong Zhang, Yong-Gang Yao

Published in: Neurogenetics | Issue 3/2010

Abstract

The primary mutation m.3460G>A occurs with a very low frequency (∼1%) in Chinese patients with Leber hereditary optic neuropathy (LHON). Up to now, there is no comprehensive study of Chinese patients harboring this mutation. We characterized six unrelated probands with m.3460G>A in this study, which were identified from 1,626 patients with LHON or suspected with LHON. The overall penetrance of LHON (25.6% [10/39]) in four pedigrees with m.3460G>A was substantially lower than those families with m.11778G>A (33.3% [619/1859]) as reported in our previous study. Intriguingly, family Le688 with a heteroplasmic m.3460G>A presented a lower penetrance (12.5%) than the other three families with a homoplasmic mutation. There is an elevated gender bias (affected male to affected female = 4:1) in the four families with m.3460G>A compared to those LHON families with m.11778G>A (2.4:1). Complete mtDNA sequencing indicated that the six matrilines belonged to haplogroups B4d1, F2, A5b, M12a, D4b2b, and D4b2, respectively. We did not identify any potential secondary mutation(s) that will affect or be associated with the penetrance of LHON in the six probands by using an evolutionary analysis and protein secondary-structure prediction. Taken together, our results suggested that the m.3460G>A mutation occurred multiple times in Chinese LHON patients. The heteroplasmic status of mutation m.3460G>A might influence the penetrance of LHON in family Le688.

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Title: Molecular characterization of six Chinese families with m.3460G>A and Leber hereditary optic neuropathy
Authors: Dandan Yu
Xiaoyun Jia
A-Mei Zhang
Xiangming Guo
Ya-Ping Zhang
Qingjiong Zhang
Yong-Gang Yao
Publication date: 01-07-2010
Publisher: Springer-Verlag
Published in: Neurogenetics / Issue 3/2010
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-010-0236-7

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Molecular characterization of six Chinese families with m.3460G>A and Leber hereditary optic neuropathy

Abstract

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Abstract

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