Infantile hepatocerebral syndromes associated with mutations in the mitochondrial DNA polymerase-γA
Infantile hepatocerebral syndromes associated with mutations in the mitochondrial DNA polymerase-γA
复制标题
DOI：
10.1093/brain/awh410
复制
发表时间：
2005-04-01
期刊：
影响因子：
14.5
通讯作者：
Zeviani, M
中科院分区：
文献类型：
--
作者：
Ferrari, G;Lamantea, E;Zeviani, M
我们研究了9名婴儿患者进行性神经和肝功能衰竭的组合。八名儿童，包括两对兄弟姐妹和四个独生子女，受到阿尔珀斯肝病性脊髓灰质炎的影响。第九名婴儿患者患有与肝衰竭相关的严重松软婴儿综合征。对编码线粒体DNA聚合酶催化亚基的基因POLG 1的分析显示，所有患者均携带该基因的不同等位基因突变。POLG1是线粒体疾病的主要致病基因。该基因的突变可能与线粒体DNA（mtDNA）的多个缺失、缺失或点突变有关。反过来，这些不同的分子表型决定了一个极其异质性的临床结果谱，从成人发作的进行性眼肌麻痹到青少年共济失调综合征伴癫痫，再到迅速致命的肝脑表现，包括阿尔珀斯综合征。
We studied nine infant patients with a combination of progressive neurological and hepatic failure. Eight children, including two sibling pairs and four singletons, were affected by Alpers' hepatopathic poliodystrophy. A ninth baby patient suffered of a severe floppy infant syndrome associated with liver failure. Analysis of POLG1, the gene encoding the catalytic subunit of mitochondrial DNA polymerase, revealed that all the patients carried different allelic mutations in this gene. POLG1 is a major disease gene in mitochondrial disorders. Mutations in this gene can be associated with multiple deletions, depletion or point mutations of mitochondrial DNA (mtDNA). In turn, these different molecular phenotypes dictate an extremely heterogeneous spectrum of clinical outcomes, ranging from adult-onset progressive ophthalmoplegia to juvenile ataxic syndromes with epilepsy, to rapidly fatal hepatocerebral presentations, including Alpers' syndrome.