Clinical and molecular features of mitochondrial DNA depletion syndromes
Clinical and molecular features of mitochondrial DNA depletion syndromes
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DOI：
10.1007/s10545-008-1038-z
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发表时间：
2009-04-01
影响因子：
4.2
通讯作者：
Zeviani, M.
中科院分区：
文献类型：
--
作者：
Spinazzola, A.;Invernizzi, F.;Zeviani, M.
线粒体DNA耗竭综合征（MDS）是一组常染色体隐性遗传疾病，其特征是受累组织中线粒体DNA拷贝数显著减少。三种主要的临床表现是已知的：肌病，脑肌病和肝脑。第一个与胸苷激酶2（TK 2）和p53诱导的核糖核苷酸还原酶B亚基（RRM 2 B）突变相关;第二个与琥珀酸合成酶A（SUCLA 2）和B（SUCLG 1）突变相关;第三个与Twinkle（PEO 1）、pol-gamma A（POLG 1）、脱氧鸟苷激酶（DGUOK）和MPV 17（MPV 17）突变相关。在这项工作中，我们回顾了MDS相关的表型，并提出了我们自己的经验，32例MDS患者，目的是定义已知基因的突变频率，疾病的临床谱，以及基因型-表型相关性。我们的五名患者携带以前未报告的突变的八个MDS基因之一。
Mitochondrial DNA depletion syndromes (MDSs) form a group of autosomal recessive disorders characterized by profoundly decreased mitochondrial DNA copy numbers in affected tissues. Three main clinical presentations are known: myopathic, encephalomyopathic and hepatocerebral. The first is associated with mutations in thymidine kinase 2 (TK2) and p53-induced ribonucleotide reductase B subunit (RRM2B); the second with mutations in succinate synthase A (SUCLA2) and B (SUCLG1); the third with mutations in Twinkle (PEO1), pol-gamma A (POLG1), deoxyguanosine kinase (DGUOK) and MPV17 (MPV17). In this work, we review the MDS-associated phenotypes and present our own experience of 32 MDS patients, with the aim of defining the mutation frequency of the known genes, the clinical spectrum of the diseases, and the genotype-phenotype correlations. Five of our patients carried previously unreported mutations in one of the eight MDS genes.