Mitochondrial mutations in maternally inherited hearing loss

Abstract

BackgroundAlthough the mitochondrial DNA (mtDNA) mutations m.1555A > G and m.3243A > G are the primary causes of maternally inherited sensorineural hearing loss (SNHL), several other mtDNA mutations are also reported to be associated with SNHL.MethodsScreening of m.1555A > G and m.3243A > G mutations was performed for 145 probands. Nine probands fulfilled the following criteria: 1) bilateral and symmetric SNHL, 2) ≥ 4 family members with SNHL with a maternal trait of inheritance in ≥ 2 generations, 3) onset of SNHL before the age of 40 years, 4) high-frequency SNHL, and 5) no record of environmental factors related to SNHL. Sequencing of additional mtDNA regions was performed for five subjects meeting the clinical criteria, but the screening results were negative.ResultsAmong the nine cases meeting the five clinical criteria detailed above, three had the m.1555A > G mutation in MTRNR1, one had a m.3243A > G mutation in MTTL1, and one case had a m.7511T > C mutation in MTTS1. In the family with the m.7511T > C mutation, penetrance of SNHL among maternally related subjects was 9/17 (53%). The age at onset varied from birth (congenital) to adulthood. Hearing levels varied from normal to moderately impaired, unlike previously reported subjects with this mutation, where some maternal family members presented with profound SNHL. Family members with the m.7511T > C mutation and SNHL did not exhibit any specific clinical characteristics distinct from those of other individuals with SNHL and different mtDNA mutations. Among the 136 probands who did not meet the criteria detailed above, one case had the m.1555A > G mutation, and three cases had the m.3243A > G mutation.ConclusionsSince five of nine probands with the clinical criteria used in this study had mtDNA mutations, these criteria may be helpful for identification of candidate patients likely to have mtDNA mutations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-017-0389-4) contains supplementary material, which is available to authorized users.

Mutation analysis of common deafness genes among 1,201 patients with non‐syndromic hearing loss in Shanxi Province

“…It has been estimated that approximately 20% of inherited postlingual deafness may be connected with mutations in the mitochondrial genome, but large ethnic variations might be present (Fan, Zhu, Tang, & Xue, ; Mutai et al, ). Fifteen patients were found to carry the c.1555A>G homoplasmic mutation in this study, accounting for 1.25% (15/1,201).…”

“…Mutations of mitochondrial DNA (mtDNA) are associated with maternally inherited sensorineural hearing loss. The mtDNA of human is double-stranded, encoding 13 protein subunits, two ribosomal RNAs (rRNAs), and 22 transfer RNAs (tRNAs) (Alves, Calmeiro, Calmeiro, Macario, & Silva, 2017;Mutai, Watabe, Watabe, Kosaki, Ogawa, & Matsunaga, 2017). The c.1555A>G is the most frequent mutation in mtDNA associated with HL.…”

Circulating cell free DNA and miRNA Amount in Congenital Hearing Loss

“…However, A1555G mutations in the mitochondrial subunit of the 12s rRNA have shown increased susceptibility to ototoxic injury caused by aminoglycosides [6]. When we took a look at literature, mit DNA mutation has been found to be high in children with congenital hearing loss [30][31], but we didn't find any research about miRNA, free DNA and hearing loss , therefore, our research is important.…”

Mitochondrial dysfunction and its role in tissue-specific cellular stress

“…Hearing loss is one of the most prevalent sensory disorders 61. Genetic factors are thought to account for more than half of congenital and childhood-onset hearing loss, including mutations in mtDNA 62 and mitochondrial nuclear genes like the heme A biogenesis factor COX10 6364 or the AAA protease responsible for complex III assembly BSC1L 6566.…”