Mitochondrial DNA. Part B. Resources (Jul 2019)

Frequency and spectrum of MT-TT variants associated with Leber’s hereditary optic neuropathy in a Chinese cohort of subjects

  • Yuanyuan Lyu,
  • Man Xu,
  • Jie Chen,
  • YanChun Ji,
  • Min-Xin Guan,
  • Juanjuan Zhang

DOI
https://doi.org/10.1080/23802359.2019.1627921
Journal volume & issue
Vol. 4, no. 2
pp. 2266 – 2280

Abstract

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Leber’s hereditary optic neuropathy (LHON) is a maternally inherited eye disease. In our previous investigations, we have reported the spectrum and frequency of mitochondrial MT-ND1, MT-ND4 and MT-ND6 gene in Chinese LHON population. This study aimed to assess the molecular epidemiology of MT-TT mutations in Chinese families with LHON. A cohort of 352 Chinese Han probands lacking the known LHON-associated mtDNA mutations and 376 control subjects underwent molecular analysis of mtDNA. All variants were evaluated for evolutionary conservation, structural and functional consequences. Fifteen variants were identified in the MT-TT gene by mitochondrial genome analysis of LHON pedigrees, which was substantially higher than that of individuals from general Chinese populations. The incidences of the two known LHON-associated mutations, m.15927G > A and m.15951A > G, were 2.27% and 1.14%, respectively. Nine putative LHON-associated variants were identified in 20 probands, translated into 2.1% cases of this cohort. Moreover, mtDNAs in 41 probands carrying the MT-TT mutation(s) were widely dispersed among nine Eastern Asian haplogroups. Our results suggest that the MT-TT gene is a mutational hotspot for these 352 Chinese families lacking the known LHON-associated mutations. These data further showed the molecular epidemiology of MT-TT mutations in Chinese Han LHON pedigrees.

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