1. Late onset nonsyndromic hearing loss in a Dongxiang Chinese family is associated with the 593T>C variant in the mitochondrial tRNA Phe gene.
- Author
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Chen X, Nie Z, Wang F, Wang J, Liu XW, Zheng J, Guo YF, and Guan MX
- Subjects
- Adenosine Triphosphate biosynthesis, Adult, Aged, Aged, 80 and over, Asian People, Child, Deafness pathology, Female, Humans, Late Onset Disorders pathology, Male, Middle Aged, Mitochondria genetics, Mitochondria metabolism, Protein Biosynthesis, Young Adult, Deafness genetics, Family Health, Genes, Mitochondrial, Late Onset Disorders genetics, Point Mutation, RNA, Transfer, Phe genetics
- Abstract
We report here the clinical, genetic, molecular and biochemical characterization of a four-generation Dongxiang Chinese pedigree with suggestively maternally transmitted non-syndromic hearing loss. Five of 10 matrilineal relatives exhibited variable severity and age at onset of sensorineural hearing loss. The average ages at onset of hearing loss in matrilineal relatives of this family were 29years. Molecular analysis of their mitochondrial genomes identified the tRNA
Phe 593T>C variant belonging to Asian haplogroup G2a2a. The m.593T>C variant resided at the position 17 of DHU-loop, where the position is important for the structure and function of tRNA. It was anticipated that the m.593T>C variant altered the structure and function of tRNAPhe . By using lymphoblastoid cell lines derived from the Chinese family, we showed a 46% decreases in the steady-state level of tRNAPhe in mutant cell lines. Western blotting analysis showed ∼35% reduction in the levels of mitochondrial translation in mutant cell lines carrying the m.593T>C variant. Impaired mitochondrial translation is apparently a primary contributor to the marked reduction in the rate of respiratory capacity. The respiratory deficiency lowed mitochondrial ATP production in the mutant cell lines. These data provide the evidence that mitochondrial dysfunctions caused by the m.593T>C variant lead to late-onset nonsyndromic hearing loss. Thus, our findings may provide the new insights into the understanding of pathophysiology and valuable information for management and treatment of maternally inherited hearing loss., (Copyright © 2017. Published by Elsevier B.V.)- Published
- 2017
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