Heteroplasmy and phenotype spectrum of the mitochondrial tRNALeu (UUR) gene m.3243A > G mutation in seven Han Chinese families
Heteroplasmy and phenotype spectrum of the mitochondrial tRNALeu (UUR) gene m.3243A > G mutation in seven Han Chinese families
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DOI：
10.1016/j.jns.2019.116562
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发表时间：
2020-01-15
影响因子：
4.4
通讯作者：
Du, Ailian
中科院分区：
文献类型：
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作者：
Liu, Gailing;Shen, Xiya;Du, Ailian
线粒体tRNA(Leu) （(UUR)）基因m.3243A > G突变与多种表型异质性相关。中国患者的临床谱和表型-基因型相关性尚不清楚。在本研究中，我们报道了携带m.3243A >g突变的7个汉族家庭的临床和遗传特征，以及单倍群。在39例母系个体中，5例患有线粒体脑肌病、乳酸酸中毒和卒中样发作（MELAS）， 2例患有危及生命的线粒体肌病（LTMM）， 1例患有神经病变、共济失调和视网膜色素变性（NARP）样综合征。LTMM和NARP样综合征丰富了m.3243A >g突变的表型谱。m.3243A >g突变的异质性在MELAS中为16% - 59%，在LTMM中为29% - 79%，在narp样综合征患者中为57%。在表现为纯粹糖尿病和纯粹听力损失的患者中，该水平为0%至14%，在13名正常家庭成员中为0%至5%。然而，我们特别注意到，在一个LTMM家族中，4名无症状个体的异质性携带的异质性突变范围为22%至78%，这意味着该家族中存在其他修饰因素。mtDNA突变的表型调节需要进一步研究。
The m.3243A > G mutation in the mitochondrial tRNA(Leu) ((UUR)) gene is associated with a variety of phenotypic heterogeneity. The clinical spectrum and phenotypic-genotypic correlations in the Chinese patients are poorly understood. In the present study, we reported the clinical and genetic characterization, as well as haplogroups of seven Han Chinese families carrying the m.3243A > G mutation. Of the 39 matrilineal individuals, five suffered from mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), two had life-threatening mitochondrial myopathy (LTMM), and one patient had neuropathy, ataxia, and retinitis pigmentosa (NARP)-like syndrome. The LTMM and NARP like syndromes enriched the phenotypic profile of the m.3243A > G mutation. The heteroplasmy of the m.3243A > G mutation ranged from 16% to 59% in MELAS, 29% to 79% in LTMM, and 57% in a NARP-like syndrome patient. The levels ranged from 0% to 14% in patients that manifested with pure diabetes and pure hearing loss, and 0% to 5% in 13 normal family members. However, we particularly noticed heteroplasmy in four asymptomatic individuals in one LTMM family carried the heteroplasmy mutation ranged from 22% to 78%, implying that there were other modifying factors in this family. The modulation of the phenotype of mtDNA mutations requires further investigation.