POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion
POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion
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DOI：
10.1002/ana.20079
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发表时间：
2004-05-01
影响因子：
11.2
通讯作者：
Nguyen, KV
中科院分区：
文献类型：
--
作者：
Naviaux, RK;Nguyen, KV
阿尔珀斯综合征是一种致命的神经遗传性疾病，70多年前首次被描述。它是一种常染色体隐性遗传的发育性线粒体DNA耗竭性疾病，特征为线粒体DNA聚合酶γ（POLG）催化活性缺乏、难治性癫痫发作、神经变性和肝病。在两个不相关的Alpers综合征家系中，发现每个受影响的儿童在POLG基因座的外显子17中携带纯合突变，导致该蛋白质聚合酶结构域上游的Glu873Stop突变。此外，每个受影响的儿童都是外显子7中G1681A突变的杂合子，该突变导致POLG蛋白质连接区内的Ala467Thr取代。
Alpers' syndrome is a fatal neurogenetic disorder first described more than 70 years ago. It is an autosomal recessive, developmental mitochondrial DNA depletion disorder characterized by deficiency in mitochondrial DNA polymerase gamma (POLG) catalytic activity, refractory seizures, neurodegeneration, and liver disease. In two unrelated pedigrees of Alpers' syndrome, each affected child was found to carry a homozygous mutation in exon 17 of the POLG locus that led to a Glu873Stop mutation just upstream of the polymerase domain of the protein. In addition, each affected child was heterozygous for the G1681A mutation in exon 7 that led to an Ala467Thr substitution in POLG, within the linker region of the protein.