Analysis of mitochondrial A1555G mutation in infants with hearing impairment

Wu,Lihua; Li,Ruiyu; Chen,Juan; Chen,Yanping; Yang,Meijun; Wu,Qing

doi:10.3892/etm.2018.6078

Analysis of mitochondrial A1555G mutation in infants with hearing impairment

Authors:
- Lihua Wu
- Ruiyu Li
- Juan Chen
- Yanping Chen
- Meijun Yang
- Qing Wu
View Affiliations

Affiliations: Department of Otolaryngology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian 350001, P.R. China, Department of Obstetrics, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian 350001, P.R. China, Department of Neonatology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian 350001, P.R. China, Department of Neonatology, Fujian Provincial Maternal and Child Health Care Hospital, Fuzhou, Fujian 350001, P.R. China
Published online on: April 18, 2018 https://doi.org/10.3892/etm.2018.6078
Pages: 5307-5313
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Mutations in the mitochondrial 12S ribosomal RNA gene have been identified to be associated with deafness. Among these, the A to G transition at position 1555 is one of the most common pathogenic mutations associated with hearing loss. In order to evaluate the allele frequency of this mutation in infants with hearing loss, the A1555G mutation was screened in 300 deaf children and 100 age‑ and sex‑matched healthy subjects. Consequently, 5 patients with this mutation were identified, whereas the mutation was absent in healthy controls. Among the patients with the mutation, only one had an obvious family history of hearing impairment. Notably, this pedigree manifested a high penetrance of deafness. In particular, the penetrance of deafness was 80 and 40%, when the aminoglycoside antibiotics (AmAn) was included or excluded, respectively. Clinical evaluation of this family exhibited a wide degree of hearing loss. Furthermore, screening for the complete mitochondrial genes revealed the occurrence of A1555G and transfer (t)RNAThr T15943C mutations, together with other genetic variations belonging to East Asian haplogroup C. Notably, the T15943C mutation, located at the T arm of tRNAThr, could disrupt the 63T‑55A base‑pairing and impair tRNA metabolism. Therefore, it was hypothesized that the combination of A1555G and T15943C mutations may result in mitochondrial dysfunction that is responsible for deafness. Screening for A1555G, as well as other potential pathogenic mutations in the mitochondrial genome, is critical for clinical diagnosis and prevention of hearing impairment.

View Figures

View References

1	Morton ME: Genetic epidemiology of hearing impairment. Ann NY Acad Sci. 630:16–31. 1991. View Article : Google Scholar : PubMed/NCBI
2	Bitner-Glindzicz M, Rahman S, Chant K and Marlow N: Gentamicin, genetic variation and deafness in preterm children. BMC Pediatr. 14:662014. View Article : Google Scholar : PubMed/NCBI
3	Fischel-Ghodsian N: Genetic factors in aminoglycoside toxicity. Pharmacogenomics. 6:27–36. 2005. View Article : Google Scholar : PubMed/NCBI
4	Prezant TR, Agapian JV, Bohlman MC, Bu X, Oztas S, Qiu WQ, Arnos KS, Cortopassi GA, Jaber L, Rotter JI, et al: Mitochondrial ribosomal RNA mutation associated with both antibiotic induced and non-syndromic deafness. Nat Genet. 4:289–294. 1993. View Article : Google Scholar : PubMed/NCBI
5	Li R, Greinwald JH Jr, Yang L, Choo DI, Wenstrup RJ and Guan MX: Molecular analysis of mitochondrial 12S rRNA and tRNASer(UCN) genes in paediatric subjects with non-syndromic hearing loss. J Med Genet. 41:615–620. 2004. View Article : Google Scholar : PubMed/NCBI
6	Neefs JM, Van de Peer Y, De Rijk P, Goris A and De Wachter R: Compilation of small ribosomal subunit RNA sequences. Nucleic Acids Res. 19 Suppl:S1987–S2015. 1991. View Article : Google Scholar
7	O'Connor M, Thomas CL, Zimmermann RA and Dahlberg AE: Decoding fidelity at the ribosomal A and P sites: Influence of mutations in three different regions of the decoding domain in 16S rRNA. Nucleic Acids Res. 25:1185–1193. 1997. View Article : Google Scholar : PubMed/NCBI
8	Zwieb CD, Jemiolo DK, Jacob WF, Wagner R and Dahlberg AE: Characterization of a collection of deletion mutants at the 3′ end of 16S ribosomal RNA of Escherichia coli. Mol Gen Genet. 203:256–264. 1986. View Article : Google Scholar : PubMed/NCBI
9	Qian Y and Guan MX: Interaction of aminoglycosides with human mitochondrial 12S rRNA carrying the deafness-associated mutation. Antimicrob Agents Chemother. 53:4612–4618. 2009. View Article : Google Scholar : PubMed/NCBI
10	Guan MX, Fischel-Ghodsian N and Attardi G: Biochemical evidence for nuclear gene involvement in phenotype of non-syndromic deafness associated with mitochondrial 12S rRNA mutation. Hum Mol Genet. 5:963–971. 1996. View Article : Google Scholar : PubMed/NCBI
11	Rieder MJ, Taylor SL, Tobe VO and Nickerson DA: Automating the identification of DNA variations using quality-based fluorescence re-sequencing: Analysis of the human mitochondrial genome. Nucleic Acids Res. 26:967–973. 1998. View Article : Google Scholar : PubMed/NCBI
12	Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM and Howell N: Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet. 23:1471999. View Article : Google Scholar : PubMed/NCBI
13	Ruiz-Pesini E and Wallace DC: Evidence for adaptive selection acting on the tRNA and rRNA genes of human mitochondrial DNA. Hum Mutat. 27:1072–1081. 2006. View Article : Google Scholar : PubMed/NCBI
14	Dai ZY, Sun BC, Huang SS, Yuan YY, Zhu YH, Su Y and Dai P: Correlation analysis of phenotype and genotype of GJB2 in patients with non-syndromic hearing loss in China. Gene. 570:272–276. 2015. View Article : Google Scholar : PubMed/NCBI
15	Guan MX, Yan Q, Li X, Bykhovskaya Y, Gallo-Teran J, Hajek P, Umeda N, Zhao H, Garrido G, Mengesha E, et al: Mutation in TRMU related to transfer RNA modification modulates the phenotypic expression of the deafness-associated mitochondrial 12S ribosomal RNA mutations. Am J Hum Genet. 79:291–302. 2006. View Article : Google Scholar : PubMed/NCBI
16	Ding Y, Li Y, You J, Yang L, Chen B, Lu J and Guan MX: Mitochondrial tRNA(Glu) A14693G variant may modulate the phenotypic manifestation of deafness-associated 12S rRNA A1555G mutation in a Han Chinese family. J Genet Genomics. 36:241–250. 2009. View Article : Google Scholar : PubMed/NCBI
17	Gruber AR, Lorenz R, Bernhart SH, Neuböck R and Hofacker IL: The vienna RNA website. Nucleic Acids Res. 36:(Web Server Issue). W70–W74. 2008. View Article : Google Scholar : PubMed/NCBI
18	Bibb MJ, Van Etten RA, Wright CT, Walberg MW and Clayton DA: Sequence and gene organization of mouse mitochondrial DNA. Cell. 26:167–180. 1981. View Article : Google Scholar : PubMed/NCBI
19	Gadaleta G, Pepe G, De Candia G, Quagliariello C, Sbisà E and Saccone C: The complete nucleotide sequence of the Rattus norvegicus mitochondrial genome: Cryptic signals revealed by comparative analysis between vertebrates. J Mol Evol. 28:497–516. 1989. View Article : Google Scholar : PubMed/NCBI
20	Roe A, Ma DP, Wilson RK and Wong JF: The complete nucleotide sequence of the Xenopus laevis mitochondrial genome. J Biol Chem. 260:9759–9774. 1985.PubMed/NCBI
21	Purohit P and Stern S: Interactions of a small RNA with antibiotic and RNA ligands of the 30S subunit. Nature. 370:659–662. 1994. View Article : Google Scholar : PubMed/NCBI
22	Hamasaki K and Rando RR: Specific binding of aminoglycosides to a human rRNA construct based on a DNA polymorphism, which causes aminoglycoside-induced deafness. Biochemistry. 36:12323–12328. 1997. View Article : Google Scholar : PubMed/NCBI
23	Usami S, Abe S, Akita J, Namba A, Shinkawa H, Ishii M, Iwasaki S, Hoshino T, Ito J, Doi K, et al: Prevalence of mitochondrial gene mutations among hearing impaired patients. J Med Genet. 37:38–40. 2000. View Article : Google Scholar : PubMed/NCBI
24	Hutchin T, Haworth I, Higashi K, Fischel-Ghodsian N, Stoneking M, Saha N, Arnos C and Cortopassi G: A molecular basis for human hypersensitivity to aminoglycoside antibiotics. Nuclear Acids Res. 21:4174–4179. 1993. View Article : Google Scholar
25	Li Z, Li R, Chen J, Liao Z, Zhu Y, Qian Y, Xiong S, Heman-Ackah S, Wu J, Choo DI and Guan MX: Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside-induced and non-syndromic hearing loss. Hum Genet. 117:9–15. 2005. View Article : Google Scholar : PubMed/NCBI
26	Lu J, Li Z, Zhu Y, Yang A, Li R, Zheng J, Cai Q, Peng G, Zheng W, Tang X, et al: Mitochondrial 12S rRNA variants in 1642 Han Chinese pediatric subjects with aminoglycoside-induced and nonsyndromic hearing loss. Mitochondrion. 10:380–390. 2010. View Article : Google Scholar : PubMed/NCBI