Mitochondrial mutations in maternally inherited hearing loss

BMC Medical Genetics

Research Article

Kenjiro Kosaki¹  Takahisa Watabe²  Kaoru Ogawa²  Tatsuo Matsunaga³  Hideki Mutai³ 

[1] Center for Medical Genetics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, 160-8582, Tokyo, Japan;Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, 160-8582, Tokyo, Japan;Division of Hearing and Balance Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro, 152-8902, Tokyo, Japan;

关键词: Mitochondrial deafness;    Maternal inheritance;    MTTS1;   

DOI  :  10.1186/s12881-017-0389-4

 received in 2016-05-31, accepted in 2017-03-02,  发布年份 2017

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s). 2017