Late onset nonsyndromic deafness in a Dongxiang Chinese family is associated with the 593T>C variant in the mitochondrial tRNA(Phe) gene.

Late onset nonsyndromic deafness in a Dongxiang Chinese family is associated with the 593T>C variant in the mitochondrial tRNA(Phe) gene.

Mitochondrion. 2017 Jun 01;:

Authors: Chen X, Nie Z, Wang F, Wang J, Liu XW, Zheng J, Guo YF, Guan MX

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 tRNA(Phe). By using lymphoblastoid cell lines derived from the Chinese family, we showed a 46% decreases in the steady-state level of tRNA(Phe) 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 deafness. 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.

PMID: 28579530 [PubMed - as supplied by publisher]

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