Mitochondrial tRNAGlu A14693G variant may modulate the phenotypic manifestation of deafness-associated 12S rRNA A1555G mutation in a Han Chinese family

Yu Ding^{a, #},
Yongyan Li^{a, #},
Junyan You^{a, #},
Li Yang^b,
Bobei Chen^c,
Jianxin Lu^a,
Min-Xin Guan^{a, b, d
, ,}

a.
Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou 325025, China
b.
Division of Human Genetics and Center for Hearing and Deafness Research, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA
c.
Department of Otolaryngology, the Second Affiliated Hospital, Wenzhou Medical College, Wenzhou 325000, China
d.
Deparment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA

More Information

Corresponding author: E-mail address: gminxin88@gmail.com (Min-Xin Guan)

These authors contributed equally to this work

摘要

- /
- /
- /
- /
- /
- /
Abstract: Mutations in mitochondrial 12S rRNA gene are one of the most important causes of aminoglycoside-induced and nonsyndromic hearing loss. Here we report the characterization of one Han Chinese pedigree with aminoglycoside-induced and nonsyndromic hearing loss. This Chinese family carrying the 12S rRNA A1555G mutation exhibited high penetrance and expressivity of hearing impairment. In particular, penetrances of hearing loss in this family pedigree were 43.8% and 25%, respectively, when aminoglycoside-induced hearing loss was included or excluded. Mutational analysis of entire mitochondrial genomes in this family showed the homoplasmic A1555G mutation and a set of variants belonging to haplogroup Y2. Of these, the A14693G variant occurred at the extremely conserved nucleotide (conventional position 54) of the TΨC-loop of tRNA^Glu and was absent in 156 Chinese controls. Nucleotides at position 54 of tRNAs are often modified, thereby contributing to the structural formation and stabilization of functional tRNAs. Thus, the structural alteration of tRNA by the A14693G variant may lead to a failure in tRNA metabolism and impair mitochondrial protein synthesis, thereby worsening mitochondrial dysfunctions altered by the A1555G mutation. Therefore, the tRNA^Glu A14693G variant may have a potential modifier role in increasing the penetrance and expressivity of the deafness-associated A1555G mutation in this Chinese pedigree.
- hearing loss /
- mitochondrial DNA /
- mutation /
- modifier /
- 12S rRNA /
- tRNA /
- Chinese family
These authors contributed equally to this work
注释:

HTML全文

参考文献(41)

[1]	Abe, S., Kelley, P.M., Kimberling, W.J. et al. Am. J. Med. Genet., 103 (2001),pp. 334-338
[2]	Andrews, R.M., Kubacka, I., Chinnery, P.F. et al. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA Nat. Genet., 23 (1999),p. 147
[3]	Bibb, M.J., Van Etten, R.A., Wright, C.T. et al. Sequence and gene organization of mouse mitochondrial DNA Cell, 26 (1981),pp. 167-180
[4]	Björk, G.R.
[5]	Brandon, M.C., Lott, M.T., Nguyen, K.C. et al. MITOMAP: A human mitochondrial genome database—2004 update Nucleic Acids Res., 33 (2005),pp. D611-D613
[6]	Chen, B., Sun, D., Yang, L. et al. Mitochondrial ND5 T12338C, tRNACys T5802C, and tRNAThr G15927A variants may have a modifying role in the phenotypic manifestation of deafness-associated 12S rRNA A1555G mutation in three Han Chinese pedigrees Am. J. Med. Genet. A, 146A (2008),pp. 1248-1258
[7]	del Castillo, F.J., Rodriguez-Ballesteros, M., Martin, Y. et al. Heteroplasmy for the 1555A>G mutation in the mitochondrial 12S rRNA gene in six Spanish families with non-syndromic hearing loss J. Med. Genet., 40 (2003),pp. 632-636
[8]	Dai, P., Liu, X., Han, D. et al. Extremely low penetrance of deafness associated with the mitochondrial 12S rRNA mutation in 16 Chinese families: Implication for early detection and prevention of deafness Biochem. Biophys. Res. Commun., 340 (2006),pp. 194-199
[9]	Enríquez, J.A., Attardi, G. Analysis of aminoacylation of human mitochondrial tRNAs Methods Enzymol., 264 (1996),pp. 183-196
[10]	Estivill, X., Govea, N., Barcelo, E. et al. Familial progressive sensorineural deafness is mainly due to the mtDNA A1555G mutation and is enhanced by treatment with aminoglycosides Am. J. Hum. Genet., 62 (1998),pp. 27-35
[11]	Fischel-Ghodsian, N. Genetic factors in aminoglycoside toxicity Pharmacogenomics, 6 (2005),pp. 27-36
[12]	Florentz, C., Sohm, B., Tryoen-Toth, P. et al. Human mitochondrial tRNAs in health and disease Cell Mol. Life Sci., 60 (2003),pp. 1356-1375
[13]	Gadaleta, G., Pepe, G., De Candia, G. et al. J. Mol. Evol., 28 (1989),pp. 497-516
[14]	Guan, M.X. Prevalence of mitochondrial 12S rRNA mutations associated with aminoglycoside ototoxicity Volta Rev., 105 (2005),pp. 211-237
[15]	Guan, M.X., Fischel-Ghodsian, N., Attardi, G. Biochemical evidence for nuclear gene involvement in phenotype of non-syndromic deafness associated with mitochondrial 12S rRNA mutation Hum. Mol. Genet., 5 (1996),pp. 963-997
[16]	Guan, M.X., Enriquez, J.A., Fischel-Ghodsian, N. et al. Mol. Cell Biol., 18 (1998),pp. 5868-5879
[17]	Guan, M.X., Fischel-Ghodsian, N., Attardi, G. A biochemical basis for the inherited susceptibility to aminoglycoside ototoxicity Hum. Mol. Genet., 9 (2000),pp. 1787-1793
[18]	Guan, M.X., Fischel-Ghodsian, N., Attardi, G. Nuclear background determines biochemical phenotype in the deafness-associated mitochondrial 12S rRNA mutation Hum. Mol. Genet., 10 (2001),pp. 573-580
[19]	Guan, M.X., Yan, Q., Li, X. et al. Am. J. Hum. Genet., 79 (2006),pp. 291-302
[20]	Li, R., Greinwald, J.H., Yang, L. et al. J. Med. Genet., 41 (2004),pp. 615-620
[21]	Li, R., Xing, G., Yan, M. et al. Cosegregation of C-insertion at position 961 with A1555G mutation of mitochondrial 12S rRNA gene in a large Chinese family with maternally inherited hearing loss Am. J. Med. Genet., 124A (2004),pp. 113-117
[22]	Li, X., Fischel-Ghodsian, N., Schwartz, F. et al. Nucleic Acids Res., 32 (2004),pp. 867-877
[23]	Li, R., Ishikawa, K., Deng, J.H. et al. Biochem. Biophys. Res. Commun., 328 (2005),pp. 32-37
[24]	Li, Z., Li, R., Chen, J. et al. Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside induced and non-syndromic hearing loss Hum. Genet., 117 (2005),pp. 9-15
[25]	Matthijs, G., Claes, S., Longo-Bbenza, B. et al. Non-syndromic deafness associated with a mutation and a polymorphism in the mitochondrial 12S ribosomal RNA gene in a large Zairean pedigree Eur. J. Hum. Genet., 4 (1996),pp. 46-51
[26]	Prezant, T.R., Agapian, J.V., Bohlman, M.C. et al. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness Nat. Genet., 4 (1993),pp. 289-294
[27]	Rieder, M.J., Taylor, S.L., Tobe, V.O. et al. Automating the identification of DNA variations using quality-based fluorescence re-sequ: Analysis of the human mitochondrial genome Nucleic Acids Res., 26 (1998),pp. 967-973
[28]	Roe, A., Ma, D.P., Wilson, R.K. et al. J. Biol. Chem., 260 (1985),pp. 9759-9774
[29]	Sprinzl, M., Horn, C., Brown, M. et al. Compilation of tRNA sequences and sequences of tRNA genes Nucleic Acids Res., 26 (1998),pp. 148-153
[30]	Sternberg, D., Chatzoglou, E., Laforet, P. et al. Mitochondrial DNA transfer RNA gene sequence variations in patients with mitochondrial disorders Brain, 124 (2001),pp. 984-994
[31]	Tanaka, M., Cabrera, V.M., González, A.M. et al. Mitochondrial genome variation in eastern Asia and the peopling of Japan Genome Res., 14 (2004),pp. 1832-1850
[32]	Tang, X., Yang, L., Zhu, Y. et al. Very low penetrance of hearing loss in seven Han Chinese pedigrees carrying the deafness-associated 12S rRNA A1555G mutation Gene, 293 (2007),pp. 11-19
[33]	Tong, Y., Mao, Y., Zhou, X. et al. Biochem. Biophys. Res. Commun., 357 (2007),pp. 524-530
[34]	Torroni, A., Petrozzi, M., D'Urbano, L. et al. Haplotype and phylogenetic analyses suggest that one European-specific mtDNA background plays a role in the expression of Leber hereditary optic neuropathy by increasing the penetrance of the primary mutations 11778 and 14484 Am. J. Hum. Genet., 60 (1997),pp. 1107-1121
[35]	Tzen, C.Y., Thajeb, P., Wu, T.Y. et al. Muscle Nerve, 28 (2003),pp. 575-581
[36]	Usami, S.I., Abe, S., Kasai, M. et al. Genetic and clinical features of sensorineural hearing loss associated with the 1555 mitochondrial mutation Laryngoscope, 107 (1997),pp. 483-490
[37]	Wang, X., Lu, J., Zhu, Y. et al. Mitochondrial tRNAThr G15927A mutation may modulate the phenotypic manifestation of ototoxic 12S rRNA A1555G mutation in four Chinese families Pharmacogenet. Genomics, 18 (2008),pp. 1059-1070
[38]	Young, W.Y., Zhao, L., Qian, Y. et al. Extremely low penetrance of hearing loss in four Chinese families with the mitochondrial 12S rRNA A1555G mutation Biochem. Biophys. Res. Commun., 328 (2005),pp. 1244-1251
[39]	Young, W.Y., Zhao, L., Qian, Y. et al. Am. J. Med. Genet., 140 (2006),pp. 2188-2197
[40]	Yuan, H., Qian, Y., Xu, Y. et al. Am. J. Med. Genet., 138A (2005),pp. 133-140
[41]	Zhao, L., Wang, Q., Qian, Y. et al. Clinical evaluation and mitochondrial genome sequence analysis of two Chinese families with aminoglycoside-induced and nonsyndromic hearing loss Biochem. Biophys. Res. Commun., 336 (2005),pp. 967-973