Longitudinal changes of mtDNA A3243G mutation load and level of functioning in MELAS.
Longitudinal changes of mtDNA A3243G mutation load and level of functioning in MELAS.
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DOI：
10.1002/ajmg.a.32703
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发表时间：
2009-02-15
影响因子：
2
通讯作者：
DiMauro, Salvatore
中科院分区：
文献类型：
--
作者：
Mehrazin, Mahsa;Shanske, Sara;Kaufmann, Petra;Wei, Ying;Coku, Jorida;Engelstad, Kristin;Naini, Ali;De Vivo, Darryl C.;DiMauro, Salvatore
线粒体脑病、乳酸酸中毒和中风样发作（MELAS）是最常见的线粒体多系统疾病之一，最常见的与线粒体DNA中核苷酸位置3243（A3243 G）处的A至G转变相关。我们研究了34名携带A3243 G突变的个体长达7年; 17名具有完整的MELAS表型，17名被归类为“携带者亲属”，因为他们要么无症状，要么有一些提示线粒体疾病的症状，但没有癫痫发作或中风。使用灵敏的实时聚合酶链反应定量A3234 G突变，我们证实了从血液中分离的DNA中突变百分比逐渐下降：完全症状患者的平均百分比下降为每年0.5%，而症状轻微的携带者亲属的平均百分比下降为每年0.2%。我们还将突变负荷与通过Karnofsky评分估计的功能状态相关联：即使突变负荷降低，完全有症状的患者的功能水平也降低，而携带者亲属的功能水平基本保持不变。这项研究表明，从血液中分离的DNA中的A3243 G突变负荷既不是有用的预后，也不是功能评估。
Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), one of the most common mitochondrial multisystemic diseases, is most commonly associated with an A-to-G transition at nucleotide position 3243 (A3243G) in mitochondrial DNA. We studied 34 individuals harboring the A3243G mutation for up to 7 years; 17 had the full MELAS phenotype and 17 who were classified as “carrier relatives” because they were either asymptomatic or had some symptoms suggestive of mitochondrial disease but no seizures or strokes. Using the sensitive real-time polymerase chain reaction to quantify the A3234G mutation, we confirmed that the percent mutation decreases progressively in DNA isolated from blood: the average percent decrease was 0.5% per year for fully symptomatic patients and 0.2% per year for oligosymptomatic carrier relatives. We also correlated mutant loads with functional status estimated by the Karnofsky score: even though the mutation load decreases, the level of functioning worsens in fully symptomatic patients, whereas the level of functioning of carrier relatives remains largely unchanged. This study suggests that A3243G mutant load in DNA isolated from blood is neither useful for prognosis nor for functional assessment.
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影响因子：
64.8
作者：
GOTO, Y;NONAKA, I;HORAI, S
通讯作者：
HORAI, S
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