Prevalence of the mitochondrial 1555 A>G and 1494 C>T mutations in a community-dwelling population in Japan

Abstract

Single nucleotide polymorphisms in mitochondrial DNA, such as mitochondrial 1555 A>G (m.1555 A>G) and mitochondrial 1494 C>T (m.1494 C>T), are known to be causative mutations of nonsyndromic hearing loss following exposure to aminoglycoside antibiotics. The prevalence of the m.1555 A>G and m.1494 C>T mutations has not been reported for the general population in Japan. The purpose of this study was to investigate the prevalence of m.1555 A>G and m.1494 C>T mutations in a community-dwelling population in Japan in order to prevent aminoglycoside-induced hearing loss. We recruited participants older than 20 years of age to the Iwaki Health Promotion Project in 2014, 2015, and 2016, resulting in the recruitment of 1,683 participants. For each participant, we performed a hearing test and a genetic test for the m.1555 A>G and m.1494 C>T mutations using the TaqMan genotyping method. The m.1555 A>G mutation was detected in only 1 of the 1,683 participants (0.06%). This carrier of the m.1555 A>G mutation was a 69-year-old male with bilateral, symmetric, and high-frequency hearing loss. We provided genetic counseling and distributed a drug card advising him to avoid the administration of aminoglycoside antibiotics. In contrast, the m.1494 C>T mutation was not detected in this study population.

A Pilot Study for Return of Individual Pharmacogenomic Results to Population-Based Cohort Study Participants

“…Drugs whose efficacy and safety are affected by the genotype (hereafter referred to as target drugs) are listed in Table 2 . A previous study reported that the m.1555A>G pathogenic variant of MT-RNR1 in 1.9% of Japanese hearing-impaired patients ( n = 264) diagnosed using the invader-based genetic screen test (24) , whereas another report described that 1 in 1,683 (0.06%) individuals from the Japanese general population participating in the IWAKI Health Promotion Project was found to harbor the m.1555A>G variant according to TaqMan genotyping (25) . Therefore, we searched this variant against the file of the merged individual 4.7KJPN genotype, which resulted in the recruitment of three variant carriers for the study.…”

Mitochondrial Diseases in Hong Kong: Prevalence, Clinical characteristics and Genetic landscape

“…For instance, the m.1555A > G variant known to give rise to non-syndromic hearing impairment and aminoglycoside-induced hearing impairment was absent in our cohort despite being a well-reported variant in the literature. [42][43] It is postulated that long term management by medical professionals in the public sector may not be strongly indicated for such patients with isolated hearing impairment, and thus led to the under-representation of these patients in our cohort. Similar situations may occur for patients with other milder phenotypes of MD.…”

Mitochondrion-targeted RNA therapies as a potential treatment strategy for mitochondrial diseases

“…Two pathogenic mutations in the rRNA encoding region have been reported: m.1555A>G and m.1494C>T. 56 The mutations in the mt-RNR1 region have been associated with age-related hearing loss, aminoglycoside-induced adverse effects, and autism spectrum disorder. 57 The mutation leads to a reduction of global mitochondrial protein expression and may also be influenced by the presence of other mtDNA polymorphisms. 58 …”