Novel nucleotide changes in mutational analysis of mitochondrial 12SrRNA gene in patients with nonsyndromic and aminoglycoside-induced hearing loss

Abstract

Mitochondria have essential role in cellular energy metabolism and defects in their function lead to many metabolic diseases. Mitochondrial DNA (mtDNA) mutations have been associated with number diseases such as nonsyndromic and aminoglycoside-induced hearing loss. Mutational screening of entire 12SrRNA and tRNA (ser (UCN)) genes in 107 unrelated Iranian patients with amino glycoside-induced and nonsyndromic bilateral hearing loss by direct sequencing analysis method were performed. Twenty different homoplasmic sequence variants were identified; including fifteen common polymorphisms, two putatively pathogenic variants: m.921T>C and m.1005T>C, one 12SrRNA sequence variant m.739C>T and two nucleotides substitution; m.1245T>C and m.1545T>C. Deafness-associated mutation, m.1555A>G, was not found. In our patients we found the mutation 1005 was associated with R haplogroup. These finding show that m.1555A>G mutation is not important in our population. Nucleotide change, m.739C>T, previously reported with very low frequency. We suggested the variation of two nucleotides 1245 and 1545 that localized at conserved site of 12SrRNA may be new candidate for amino glycoside-induced and nonsyndromic hearing impairment associated mutations. However, aminoglycoside exposure is a risk factor for clinical phenotype appearance of these mutations.

Association of nuclear and mitochondrial genes with audiological examinations in Iranian patients with nonaminoglycoside antibiotics-induced hearing loss

“… 31 , 59 , 60 , 62 – 64 However, consistent with the other studies, 58 – 61 , 65 , 66 our study showed that even in the absence of aminoglycoside exposure, mitochondrial polymorphisms could be responsible for hearing impairment. Previous studies revealed the mitochondrial m1555A>G, 67 m.1005T>C, 68 and m.921T.C 68 mutations among Iranian patients, while these mentioned mutations were not detected in our patients with HL. Additionally, a study indicated the high carrier frequency of the nuclear GJB2 mutation (35delG) in the north of Iran.…”

Reactive Oxygen Species, Apoptosis, and Mitochondrial Dysfunction in Hearing Loss

“…However, the precise mechanism of aminoglycoside interaction with rRNA is still under investigation [ 46 ]. Other mutations of mitochondrial DNA associated with aminoglycoside hypersusceptible hearing loss have been found in a recent study [ 47 ].…”

The potential role for use of mitochondrial DNA copy number as predictive biomarker in presbycusis

“…A lack of introns and protective histones make mtDNA more susceptible to ROS and other types of damage, which could lead to sequence mutations or copy number alterations. 12 Variation of both quality (mutations) 13 , 14 and quantity (copy number) 15 of mtDNA has been associated with many human diseases, including neurodegenerative diseases, 16 metabolic diseases, and various types of cancer, 17 as well as in the process of aging. 18 Therefore, the application of mtDNA alteration as a biomarker in aging, age-related diseases, cancers, metabolic diseases, and even forensic science is currently being investigated.…”