pubmed.ncbi.nlm.nih.gov

Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside-induced and non-syndromic hearing loss - PubMed

️Wed Dec 13 2350

Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside-induced and non-syndromic hearing loss

Zhiyuan Li et al. Hum Genet. 2005 Jun.

Abstract

Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. We report here a systematic mutational screening of the mitochondrial 12S rRNA gene in 128 Chinese pediatric subjects with sporadic aminoglycoside-induced and non-syndromic hearing loss. We show that aminoglycoside ototoxicity accounts for 48% of cases of hearing loss in this Chinese pediatric population. Of the known deafness-associated mutations in this gene, the incidence of the A1555G mutation is approximately 13% and approximately 2.9% in this Chinese pediatric population with aminoglycoside-induced and non-syndromic hearing loss, respectively. Furthermore, mutations at position 961 in the 12S rRNA gene account for approximately 1.7% and 4.4% of cases of aminoglycoside-induced and non-syndromic hearing loss in this Chinese clinical population, respectively. The T1095C mutation has been identified in one maternally inherited family with aminoglycoside-induced and non-syndromic hearing loss. However, the C1494T mutation was not detected in this clinical population. In addition, three variants, A827G, T1005C and A1116G, in the 12S rRNA gene, localized at highly conserved sites, may play a role in the pathogenesis of aminoglycoside ototoxicity. These data strongly suggest that the mitochondrial 12S rRNA is a hot-spot for deafness-associated mutations in the Chinese population.

PubMed Disclaimer

Figures

**Fig. 1**
Qualification of the A1555G mutation in ten Chinese subjects with aminoglycoside-induced and non-syndromic hearing loss. PCR products around the A1555G region of mitochondrial genome were digested with *Bsm*AI and analyzed by electrophoresis in a 1.5% agarose gel stained with ethidium bromide. F11B is a positive control from an Arab-Israeli family (Guan et al. 1996) and A2 is a Chinese control subject (Zhao et al. 2004a)

**Fig. 2**
Three Chinese pedigrees with maternally inherited aminoglycoside-induced and non-syndromic hearing impairment. Hearing impaired individuals are indicated by *filled symbols. Arrows* denote probands. *Asterisks* denote individuals who had a history of exposure to aminoglycosides

**Fig. 3a,b**
Molecular and genetic analysis of an affected subject #110 carrying the T1095C mutation in the 12S rRNA gene. a Sequence chromatograms from an affected individual #110 and an unaffected control A2, showing the T to C transition at position 1095 (*arrow*). b A Chinese pedigree with aminoglycoside-induced and non-syndromic hearing impairment. Hearing impaired individuals are indicated by *filled symbols. Arrow* denotes subject #110

Cited by

Molecular and clinical characterisation of three Spanish families with maternally inherited non-syndromic hearing loss caused by the 1494C->T mutation in the mitochondrial 12S rRNA gene.
Rodríguez-Ballesteros M, Olarte M, Aguirre LA, Galán F, Galán R, Vallejo LA, Navas C, Villamar M, Moreno-Pelayo MA, Moreno F, del Castillo I. Rodríguez-Ballesteros M, et al. J Med Genet. 2006 Nov;43(11):e54. doi: 10.1136/jmg.2006.042440. J Med Genet. 2006. PMID: 17085680 Free PMC article.
A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness.
Bardien S, Human H, Harris T, Hefke G, Veikondis R, Schaaf HS, van der Merwe L, Greinwald JH, Fagan J, de Jong G. Bardien S, et al. BMC Med Genet. 2009 Jan 13;10:2. doi: 10.1186/1471-2350-10-2. BMC Med Genet. 2009. PMID: 19144107 Free PMC article.
Mutational analysis of whole mitochondrial DNA in patients with MELAS and MERRF diseases.
Choi BO, Hwang JH, Cho EM, Jeong EH, Hyun YS, Jeon HJ, Seong KM, Cho NS, Chung KW. Choi BO, et al. Exp Mol Med. 2010 Jun 30;42(6):446-55. doi: 10.3858/emm.2010.42.6.046. Exp Mol Med. 2010. PMID: 20440095 Free PMC article.
Leber's hereditary optic neuropathy, intellectual disability and epilepsy presenting with variable penetrance associated to the m.3460G >A mutation and a heteroplasmic expansion of the microsatellite in MTRNR1 gene - case report.
Bianco A, Bisceglia L, De Caro MF, Galeandro V, De Bonis P, Tullo A, Zoccolella S, Guerriero S, Petruzzella V. Bianco A, et al. BMC Med Genet. 2018 Jul 27;19(1):129. doi: 10.1186/s12881-018-0644-3. BMC Med Genet. 2018. PMID: 30053855 Free PMC article.
Systematic analysis of mitochondrial genes associated with hearing loss in the Japanese population: dHPLC reveals a new candidate mutation.
Mutai H, Kouike H, Teruya E, Takahashi-Kodomari I, Kakishima H, Taiji H, Usami S, Okuyama T, Matsunaga T. Mutai H, et al. BMC Med Genet. 2011 Oct 12;12:135. doi: 10.1186/1471-2350-12-135. BMC Med Genet. 2011. PMID: 21989059 Free PMC article.

References

1. Anderson S, Bankier AT, Barrell BG, deBruijn MHL, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Rose BA, Sanger F, Schreier PH, Smith AJH, Staden R, Young I. Sequence and organization of the human mitochondrial genome. Nature. 1981;290:457–465. - PubMed
1. Bacino C, Prezant TR, Bu X, Fournier P, Fischel-Ghodsian N. Susceptibility mutations in the mitochondrial small ribosomal RNA gene in aminoglycoside induced deafness. Pharmacogenetics. 1995;5:165–172. - PubMed
1. Bibb MJ, Van Etten RA, Wright CT, Walberg MW, Clayton DA. Sequence and gene organization of mouse mitochondrial DNA. Cell. 1981;26:167–180. - PubMed
1. Casano RA, Johnson DF, Bykhovskaya Y, Torricelli F, Bigozzi M, Fischel-Ghodsian N. Inherited susceptibility to aminoglycoside ototoxicity: genetic heterogeneity and clinical implications. Am J Otolaryngol. 1999;20:151–156. - PubMed
1. Chamber HF, Sande MA (1996) The aminoglycosides. In: Hardman JG, Limbird LE, Molino. PB, Ruddon RW, Gilman AG (eds) The pharmacological basis of therapeutic, 9th edn. McGraw-Hill, New York, pp 1103–1221

Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside-induced and non-syndromic hearing loss - PubMed