TY - JOUR
T1 - The prevalence of mitochondrial mutations associated with aminoglycoside-induced deafness in ethnic Latvian population
T2 - the appraisal of the evidence
AU - Igumnova, Viktorija
AU - Veidemane, Lauma
AU - Vīksna, Anda
AU - Capligina, Valentina
AU - Zole, Egija
AU - Ranka, Renate
N1 - Funding Information:
Acknowledgements We acknowledge the Genome Database of the Latvian Population for providing DNA samples used in this study. The research was supported by Latvian National Research Program VPP “BIOMEDICINE”.
Publisher Copyright:
© 2018, The Author(s) under exclusive licence to The Japan Society of Human Genetics.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Aminoglycosides are potent antibiotics which are used to treat severe gram-negative infections, neonatal sepsis, and multidrug-resistant tuberculosis. Ototoxicity is a well-known side effect of aminoglycosides, and a rapid, profound, and irreversible hearing loss can occur in predisposed individuals. MT-RNR1 gene encoding the mitochondrial ribosomal 12S subunit is a hot spot for aminoglycoside-induced hearing loss mutations, however, a variability in the nature and frequency of genetic changes in different populations exists. The objective of this study was to analyze MT-RNR1 gene mutations in a Baltic-speaking Latvian population, and to estimate the prevalence of such genetic changes in the population-specific mitochondrial haplogroups. In the cohort of 191 ethnic non-related Latvians, the presence of two deafness-associated mutations, m.1555A>G and m.827A>G, three potentially pathogenic variations, m.961insC(n), m.961T>G and m.951G>A, and one unknown substitution, m961T>A was detected, and the aggregate frequency of all variants was 7.3%. All genetic changes were detected in samples belonged to the haplogroups H, U, T, and J. The presence of several aminoglycoside ototoxicity-related MT-RNR1 gene mutations in Baltic-speaking Latvian population indicates the necessity to include ototoxicity-related mutation analysis in the future studies in order to determine the feasibility of DNA screening for patients before administration of aminoglycoside therapy.
AB - Aminoglycosides are potent antibiotics which are used to treat severe gram-negative infections, neonatal sepsis, and multidrug-resistant tuberculosis. Ototoxicity is a well-known side effect of aminoglycosides, and a rapid, profound, and irreversible hearing loss can occur in predisposed individuals. MT-RNR1 gene encoding the mitochondrial ribosomal 12S subunit is a hot spot for aminoglycoside-induced hearing loss mutations, however, a variability in the nature and frequency of genetic changes in different populations exists. The objective of this study was to analyze MT-RNR1 gene mutations in a Baltic-speaking Latvian population, and to estimate the prevalence of such genetic changes in the population-specific mitochondrial haplogroups. In the cohort of 191 ethnic non-related Latvians, the presence of two deafness-associated mutations, m.1555A>G and m.827A>G, three potentially pathogenic variations, m.961insC(n), m.961T>G and m.951G>A, and one unknown substitution, m961T>A was detected, and the aggregate frequency of all variants was 7.3%. All genetic changes were detected in samples belonged to the haplogroups H, U, T, and J. The presence of several aminoglycoside ototoxicity-related MT-RNR1 gene mutations in Baltic-speaking Latvian population indicates the necessity to include ototoxicity-related mutation analysis in the future studies in order to determine the feasibility of DNA screening for patients before administration of aminoglycoside therapy.
UR - http://www.scopus.com/inward/record.url?scp=85058011477&partnerID=8YFLogxK
U2 - 10.1038/s10038-018-0544-6
DO - 10.1038/s10038-018-0544-6
M3 - Article
C2 - 30523288
AN - SCOPUS:85058011477
SN - 1434-5161
VL - 64
SP - 199
EP - 206
JO - Journal of Human Genetics
JF - Journal of Human Genetics
IS - 3
ER -