Aminoglycoside-induced and non-syndromic hearing loss is associated with the G7444A mutation in the mitochondrial COI/tRNA{sup Ser(UCN)} genes in two Chinese families
- Department of Otolaryngology and Zhejiang Provincial Key Laboratory of Medical Genetics, First Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang (China)
- Division and Program in Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 (United States)
- Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang (China)
- Center for Hearing and Deafness Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 (United States)
We report here the clinical, genetic, and molecular characterization of two Chinese families with aminoglycoside induced and non-syndromic hearing impairment. Clinical and genetic evaluations revealed the variable severity and age-of-onset in hearing impairment in these families. Strikingly, there were extremely low penetrances of hearing impairment in these Chinese families. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the distinct sets of mtDNA polymorphism, in addition to the identical G7444A mutation associated with hearing loss. Indeed, the G7444A mutation in the CO1 gene and the precursor of tRNA{sup Ser(UCN)} gene is present in homoplasmy only in the maternal lineage of those pedigrees but not other members of these families and 164 Chinese controls. Their mitochondrial genomes belong to the Eastern Asian haplogroups C5a and D4a, respectively. In fact, the occurrence of the G7444A mutation in these several genetically unrelated subjects affected by hearing impairment strongly indicates that this mutation is involved in the pathogenesis of hearing impairment. However, there was the absence of other functionally significant mtDNA mutations in two Chinese pedigrees carrying the G7444A mutation. Therefore, nuclear modifier gene(s) or aminoglycoside(s) may play a role in the phenotypic expression of the deafness-associated G7444A mutation in these Chinese pedigrees.
- OSTI ID:
- 20798895
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 342, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2006.02.027; PII: S0006-291X(06)00317-2; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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