Mitochondrial myopathy, lactic acidosis, and sideroblastic anemia (MLASA) plus associated with a novel de novo mutation (m.8969G>A) in the mitochondrial encoded ATP6 gene
Mitochondrial myopathy, lactic acidosis, and sideroblastic anemia (MLASA) plus associated with a novel de novo mutation (m.8969G>A) in the mitochondrial encoded ATP6 gene
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DOI：
10.1016/j.ymgme.2014.06.004
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发表时间：
2014-11-01
影响因子：
3.8
通讯作者：
Scaglia, Fernando
中科院分区：
文献类型：
--
作者：
Burrage, Lindsay C.;Tang, Sha;Scaglia, Fernando
线粒体肌病、乳酸性酸中毒和成型性贫血（MLASA）是一种罕见的线粒体疾病，以前与PUS1和YARS2突变有关。在本报告中，我们描述了一个6岁的男性与MLASA +表型。该患者具有发育迟缓、感音神经性听力丧失、癫痫、胼胝体发育不全、发育不全和卒中样发作的MLASA特征。线粒体基因组测序鉴定了线粒体DNA （mtDNA）编码ATP6基因（m.8969G> a, p.S148N）的一个新的异质突变。全外显子组测序未发现PUS1或YARS2或任何已知核基因的突变或变异可能影响线粒体功能并解释这种表型。来自患者的成纤维细胞的研究显示低霉素敏感呼吸减少，这一发现与复杂的V缺陷一致。因此，MT-ATP6的这种突变可能代表了与MLASA表型相关的第一个mtDNA点突变。(C) 2014 Elsevier Inc .版权所有
Mitochondrial myopathy, lactic acidosis and sideroblastic anemia (MLASA) is a rare mitochondrial disorder that has previously been associated with mutations in PUS1 and YARS2. In the present report, we describe a 6-year old male with an MLASA plus phenotype. This patient had features of MLASA in the setting of developmental delay, sensorineural hearing loss, epilepsy, agenesis of the corpus callosum, failure to thrive, and stroke-like episodes. Sequencing of the mitochondrial genome identified a novel de novo, heteroplasmic mutation in the mitochondrial DNA (mtDNA) encoded ATP6 gene (m.8969G>A, p.S148N). Whole exome sequencing did not identify mutations or variants in PUS1 or YARS2 or any known nuclear genes that could affect mitochondrial function and explain this phenotype. Studies of fibroblasts derived from the patient revealed a decrease in oligomycin-sensitive respiration, a finding which is consistent with a complex V defect. Thus, this mutation in MT-ATP6 may represent the first mtDNA point mutation associated with the MLASA phenotype. (C) 2014 Elsevier Inc All rights reserved.