2014, Number 2
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Otorrinolaringología 2014; 59 (2)
Mitochondrial DNA Polymorphisms in Patients with Vestibular Ablation by Gentamicin
Aguilar-Maldonado B, Esteinou-Madrid MC, Meza G
Language: Spanish
References: 22
Page: 113-120
PDF size: 395.38 Kb.
ABSTRACT
Background: Aminoglycosides are a group of antibiotics with great
antimicrobial potential against severe infectious diseases and infections produced by organisms multi-resistant to other antibiotics. Their
administration should be regulated due to their toxic consequences for
auditive-vestibular and renal systems.
Objective: To identify mitochondrial DNA mutations associated to
hypersensitivity to aminoglycoside in Mexican patients.
Patients and method: A comparative study of three patients treated
with gentamicin was done. Clinical tests were performed to determine
auditory and vestibular function. Mitochondrial DNA analysis
was determined in peripheral blood samples by molecular biological
techniques. Resulting oligonucleotides were sequenced and compared
with existing normal reference sequences (rCRS) reported for human
mitochondrial DNA.
Results: Clinical studies of vestibular function of the three patients
evidenced no damage in one of the patients whereas the remaining
two showed severe vestibular affection. After a long period of rehabilitation,
only one patient of the two affected recovered vestibular function.
In none of the cases, auditory function was compromised. When
mitochondrial DNA sequences were attained, some changes were
evident in the three patients, some of them localized in the hypervariable
regions 2 and 3; the most numerous changes were found in the
patient showing no recovery of vestibular function, especially where
transcription factors bind to mitochondrial DNA, thus affecting deeply
the mitochondrial function.
Conclusion: Some of the modifications found in mitochondrial DNA
sequence can be responsible for vestibular damage caused by gentamicin
and of the absence of recovery of vestibular function.
REFERENCES
Peloquin CA, Berning SE, Nitta AT, Simone PM, et al. Aminoglycoside toxicity: daily versus thrice-weekly dosing for treatment of mycobacterial diseases. Clin Infect Dis 2004;38:1538-1544.
Gilbert DN. Once-daily aminoglycoside therapy. Antimicrob Agents Chemother 1991;35:399-405.
Higashi K. Unique inheritance of streptomycin-induced deafness. Clin Genet 1989;35:433-436.
Hutchin TP, Cortopassi GA. Mitochondrial defects and hearing loss. Cell Mol Life Sci 2000;57:1927-1937.
Kokotas H, Petersen MB, Willems PJ. Mitochondrial deafness. Clin Genet 2007;71:379-391.
Bacino C, Prezant TR, Bu X, Fournier P, et al. Susceptibility mutations in the mitochondrial small ribosomal RNA gene in aminoglycoside induced deafness. Pharmacogenetics 1995;5:165-172.
Casano RA, Johnson DF, Bykhovskaya Y, Torricelli F, et al. Inherited susceptibility to aminoglycoside ototoxicity: genetic heterogeneity and clinical implications. Am J Otolaryngol 1999;20:151-156.
Zhao L, Young WY, Li R, Wang Q, et al. Clinical evaluation and sequence analysis of the complete mitochondrial genome of three Chinese patients with hearing impairment associated with the 12S rRNA T1095C mutation. Biochem Biophys Res Commun 2004;325:1503-1508.
Bravo O, Ballana E, Estivill X. Cochlear alterations in deaf and unaffected subjects carrying the deafness-associated A1555G mutation in the mitochondrial 12S rRNA gene. Biochem Biophys Res Commun 2006;344:511-516.
Noguchi Y, Yashima T, Ito T, Sumi T, et al. Audio-vestibular findings in patients with mitochondrial A1555G mutation. Laryngoscope 2004;114:344-348.
Li Z, Li R, Chen J, Liao Z, et al. Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside-induced and non-syndromic hearing loss. Hum Genet 2005;117:9-15.
Casano RA, Bykhovskaya Y, Johnson DF, Hamon M, et al. Hearing loss due to the mitochondrial A1555G mutation in Italian families. Am J Med Genet 1998;79:388-391.
Bae JW, Lee KY, Choi SY, Lee SH, et al. Molecular analysis of mitochondrial gene mutations in Korean patients with nonsyndromic hearing loss. Int J Mol Med 2008;22:175-180.
Rodríguez-Ballesteros M, Olarte M, Aguirre LA, Galán F, et al. 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. J Med Genet 2006;43:e54.
Meza G, Torres-Ruiz NM, Tirado-Gutiérrez C, Aguilera P. mtDNA mutations, hearing loss and aminoglycoside treatment in Mexicans. Braz J Otorhinolaryngol 2011;77(5):573-576.
Chen J, Yuan H, Lu J, Liu X, et al. Mutations at position 7445 in the precursor of mitochondrial tRNA(Ser(UCN)) gene in three maternal Chinese pedigrees with sensorineural hearing loss. Mitochondrion 2008;8:285-292.
Wei Q, Xu D, Chen Z, Li H, et al. Maternally transmitted aminoglycoside-induced and non-syndromic hearing loss caused by the 1494C> T mutation in the mitochondrial 12S rRNA gene in two Chinese families. Int J Audiol 2013;52:98-103.
Muyderman H, Sims NR, Tanaka M, Fuku N, et al. The mitochondrial T1095C mutation increases gentamicin-mediated apoptosis. Mitochondrion 2012;12:465-471.
Manwaring N, Jones MM, Wang JJ, Rochtchina E, et al. Mitochondrial DNA haplogroups and age-related hearing loss. Arch Otolaryngol Head Neck Surg 2007;133:929-933.
Hutchin T, Haworth I, Higashi K, Fischel-Ghodsian N, et al. A molecular basis for human hypersensitivity to aminoglycoside antibiotics. Nucleic Acids Res 1993;21:4174-4179.
MITOMAP: Mitochondrial DNA Function Locations. Disponible en http://www.mitomap.org/bin/view.pl/ MITOMAP/GenomeLoci.
Dobie RA, Black FO, Pezsnecker SC, Stallings VL. Hearing loss in patients with vestibulotoxic reactions to gentamicin therapy. Arch Otolaryngol Head Neck Surg 2006;132:253-257.