Maternally inherited nonsyndromic hearing loss is associated with the T7511C mutation in the mitochondrial tRNASer(UCN) gene in a Japanese family

Ronghua Li, Kotaro Ishikawa, Jian Hong Deng, Selena Heman-Ackah, Yuya Tamagawa, Li Yang, Yidong Bai, Keiichi Ichimura, Min Xin Guan

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

We report here the characterization of a Japanese family with maternally transmitted nonsyndromic hearing loss. Fourteen of 21 matrilineal relatives in this family exhibited early or late-onset/progressive but noncongenital hearing impairment with a wide range of severity, ranging from severe to normal hearing. The age-of-onset varies from 3 to 30 years. Sequence analysis of the complete mitochondrial genome in one matrilineal relative of this family revealed the presence of T7511C mutation and other variants. However, the levels of heteroplasmy of T7511C mutation did not correlate with the severity and age-of-onset of hearing loss in this family. Furthermore, none of other mtDNA variants are evolutionarily conserved and implicated to have significantly functional consequence. The absence of the ND1 T3308C and tRNAAla T5655C mutations in this Japanese family but the presence of these mtDNA mutations in an African family with a high penetrance seems to account for different penetrance between two pedigrees. Incomplete penetrance in this family indicates the involvement of modulatory factors in the phenotypic expression of hearing impairment associated with the T7511C mutation. Here, two known variants G79A and G109A in the GJB2 gene were identified in the hearing-impaired and normal hearing matrilineal relatives of this Japanese family. However, the lack of correlation in the severity and age-of-onset in hearing impairment with homozygous or heterozygous G79A or G109A or combination of both variants in the GJB2 gene in those subjects with hearing impairment and normal hearing indicates that those variants of GJB2 gene may not be a modifier of the phenotypic effects of the T7511C mutation in those subjects. Thus, the phenotypic variability in this family is due to the involvement of other modifier factor(s).

Original languageEnglish (US)
Pages (from-to)32-37
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume328
Issue number1
DOIs
StatePublished - Mar 4 2005

Keywords

  • GJB2
  • Haplotype
  • Hearing loss
  • Inherited
  • Japanese
  • Mitochondria
  • Mutation
  • Penetrance
  • tRNA

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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