RT Journal Article SR Electronic T1 The novel mitochondrial 16S rRNA 2336T>C mutation is associated with hypertrophic cardiomyopathy JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 176 OP 184 DO 10.1136/jmedgenet-2013-101818 VO 51 IS 3 A1 Liu, Zhong A1 Song, Yanrui A1 Li, Dan A1 He, Xiangyu A1 Li, Shishi A1 Wu, Bifeng A1 Wang, Wei A1 Gu, Shulian A1 Zhu, Xiaoyu A1 Wang, Xuexiang A1 Zhou, Qiyin A1 Dai, Yu A1 Yan, Qingfeng YR 2014 UL http://jmg.bmj.com/content/51/3/176.abstract AB Background Hypertrophic cardiomyopathy (HCM) is a primary disorder characterised by asymmetric thickening of septum and left ventricular wall, with a prevalence of 0.2% in the general population. Objective To describe a novel mitochondrial DNA mutation and its association with the pathogenesis of HCM. Methods and results All maternal members of a Chinese family with maternally transmitted HCM exhibited variable severity and age at onset, and were implanted permanent pacemakers due to complete atrioventricular block (AVB). Nuclear gene screening (MYH7, MYBPC3, TNNT2 and TNNI3) was performed, and no potential pathogenic mutation was identified. Mitochondrial DNA sequencing analysis identified a novel homoplasmic 16S rRNA 2336T>C mutation. This mutation was exclusively present in maternal members and absent in non-maternal members. Conservation index by comparison to 16 other vertebrates was 94.1%. This mutation disturbs the 2336U-A2438 base pair in the stem–loop structure of 16S rRNA domain III, which is involved in the assembly of mitochondrial ribosome. Oxygen consumption rate of the lymphoblastoid cells carrying 2336T>C mutation had decreased by 37% compared with controls. A reduction in mitochondrial ATP synthesis and an increase in reactive oxidative species production were also observed. Electron microscopic analysis indicated elongated mitochondria and abnormal mitochondrial cristae shape in mutant cells. Conclusions It is suggested that the 2336T>C mutation is one of pathogenic mutations of HCM. This is the first report of mitochondrial 16S rRNA 2336T>C mutation and an association with maternally inherited HCM combined with AVB. Our findings provide a new insight into the pathogenesis of HCM.