Wu Lihua, Li Ruiyu, Chen Juan, Chen Yanping, Yang Meijun, Wu Qing
Department of Otolaryngology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian 350001, P.R. China.
Department of Obstetrics, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian 350001, P.R. China.
Exp Ther Med. 2018 Jun;15(6):5307-5313. doi: 10.3892/etm.2018.6078. Epub 2018 Apr 18.
Mutations in the mitochondrial 12S ribosomal RNA gene have been identified to be associated with deafness. Among these, the A to G transition at position 1555 is one of the most common pathogenic mutations associated with hearing loss. In order to evaluate the allele frequency of this mutation in infants with hearing loss, the A1555G mutation was screened in 300 deaf children and 100 age- and sex-matched healthy subjects. Consequently, 5 patients with this mutation were identified, whereas the mutation was absent in healthy controls. Among the patients with the mutation, only one had an obvious family history of hearing impairment. Notably, this pedigree manifested a high penetrance of deafness. In particular, the penetrance of deafness was 80 and 40%, when the aminoglycoside antibiotics (AmAn) was included or excluded, respectively. Clinical evaluation of this family exhibited a wide degree of hearing loss. Furthermore, screening for the complete mitochondrial genes revealed the occurrence of A1555G and transfer (t)RNA T15943C mutations, together with other genetic variations belonging to East Asian haplogroup C. Notably, the T15943C mutation, located at the T arm of tRNA, could disrupt the 63T-55A base-pairing and impair tRNA metabolism. Therefore, it was hypothesized that the combination of A1555G and T15943C mutations may result in mitochondrial dysfunction that is responsible for deafness. Screening for A1555G, as well as other potential pathogenic mutations in the mitochondrial genome, is critical for clinical diagnosis and prevention of hearing impairment.
线粒体12S核糖体RNA基因的突变已被确定与耳聋有关。其中，第1555位的A到G转换是与听力损失相关的最常见致病突变之一。为了评估该突变在听力损失婴儿中的等位基因频率，对300名失聪儿童和100名年龄及性别匹配的健康受试者进行了A1555G突变筛查。结果，鉴定出5名携带该突变的患者，而健康对照中未发现该突变。在携带该突变的患者中，只有一名有明显的听力障碍家族史。值得注意的是，这个家系表现出高耳聋外显率。特别是，当使用或不使用氨基糖苷类抗生素时，耳聋的外显率分别为80%和40%。对这个家族的临床评估显示听力损失程度差异很大。此外，对完整线粒体基因的筛查发现了A1555G和转移（t）RNA T15943C突变，以及属于东亚单倍群C的其他基因变异。值得注意的是，位于tRNA T臂的T15943C突变可能破坏63T - 55A碱基配对并损害tRNA代谢。因此，推测A1555G和T15943C突变的组合可能导致线粒体功能障碍，进而导致耳聋。筛查A1555G以及线粒体基因组中的其他潜在致病突变，对于听力障碍的临床诊断和预防至关重要。
