Mitochondrial mutations in maternally inherited hearing loss

BACKGROUND: Although 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. METHODS: Screening 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. RESULTS: Among 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. CONCLUSIONS: Since 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 MATERIAL: The online version of this article (doi:10.1186/s12881-017-0389-4) contains supplementary material, which is available to authorized users.