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Hereditas(Beijing) >

2011 , Vol. 33 >Issue 4: 322 - 328

DOI: https://doi.org/10.3724/SP.J.1005.2011.00322

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The mitochondrial ND5 T12338C mutation may be associated with Leber’s hereditary optic neuropathy in two Chinese families

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  • 1. Giuseppe Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou 325035, China 2. School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou 325027, China 3. Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati OH 45229, USA 4. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati OH 45229, USA

Received date: 2010-07-19

  Revised date: 2010-11-18

  Online published: 2011-04-25

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Abstract

Leber’s hereditary optic neuropathy (LHON) associated with mitochondrial DNA mutation is a maternally inherited eye disease. We reported here the clinical, genetic and molecular characterization of two Han Chinese families with Leber’s hereditary optic neuropathy. Ophthalmologic examinations revealed that the variable severity and age-of-onset in visual impairment among probands and other matrilineal relatives of these families. Strikingly, there were extremely low penetrances of visual impairment in these families. Sequence analysis of complete mitochondrial genomes in these pedi-grees identified the homoplasmic ND4 G11696A and ND5 T12338C mutation and distinct sets of polymor-phism belonging to haplogroups F2. It is well known that mitochondrial DNA ND4 G11696A is associated with LHON. The ND5 T12338C mutation resulted in replacement of the first amino acid, translation-initiating methion-ine with a threonine, and shortening two amino acids of ND5. This mutation also locates in two nucleotides adjacent to the 3' end of the tRNALeu(CUN). Thus, this mutation may alter structural formation and stabilization of functional tRNA, thereby leading to a failure in protein synthesis and mitochondrial dysfunction involved in visual impairment. Therefore, the ND4 G11696A and ND5 T12338C mutation is likely associated with LHON in these two Chinese families. But these families exhibited extremely low penetrances of visual impairment. It suggests that other factors, such as nuclear modifier gene(s) or environmental factor(s), may play a role in the phenotypic expression of the LHON-associated ND4 G11696A and ND5 T12338C mutation.

Key words： Leber’s hereditary optic neuropathy; visual impairment; mitochondrial DNA; penetrance; mutation

Cite this article

JI Yan-Chun, LIU Xiao-Ling, ZHAO Fu-Xin, ZHANG Juan-Juan, ZHANG Yu, ZHOU Xiang-Tian, QU Jia, GUAN Min-Xin . The mitochondrial ND5 T12338C mutation may be associated with Leber’s hereditary optic neuropathy in two Chinese families[J]. Hereditas(Beijing), 2011 , 33(4) : 322 -328 . DOI: 10.3724/SP.J.1005.2011.00322

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