Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations
Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations
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DOI：
10.1086/510023
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发表时间：
2006-12-01
影响因子：
9.8
通讯作者：
Hirano, Michio
中科院分区：
文献类型：
--
作者：
Lopez, Luis Carlos;Schuelke, Markus;Hirano, Michio
辅酶 Q(10) (CoQ(10)) 是一种重要的亲脂性分子，可将电子从线粒体呼吸链复合物 I 和 II 转移到复合物 III。 CoQ(10) 缺乏与多种临床表型相关，但大多数患者的分子原因尚不清楚。 CoQ(10) 生物合成基因 COQ2 的第一个缺陷是在一名患有脑肌病和肾病综合征的儿童以及一名仅患有肾病的弟弟妹妹中发现的。在此，我们描述了一名患有严重 Leigh 综合征、肾病综合征、肌肉和成纤维细胞 CoQ(10) 缺乏以及 PDSS2 基因复合杂合突变的婴儿，该基因编码十异丙烯基二磷酸合酶亚基，这是 CoQ(10) 生物合成途径的第一种酶。放射性标记底物的生化检测表明患者成纤维细胞中的十异戊二烯二磷酸合酶存在严重缺陷。这是对 PDSS2 致病性突变的首次描述，并证实了原发性 CoQ(10) 缺陷的分子和临床异质性。
Coenzyme Q(10) (CoQ(10)) is a vital lipophilic molecule that transfers electrons from mitochondrial respiratory chain complexes I and II to complex III. Deficiency of CoQ(10) has been associated with diverse clinical phenotypes, but, in most patients, the molecular cause is unknown. The first defect in a CoQ(10) biosynthetic gene, COQ2, was identified in a child with encephalomyopathy and nephrotic syndrome and in a younger sibling with only nephropathy. Here, we describe an infant with severe Leigh syndrome, nephrotic syndrome, and CoQ(10) deficiency in muscle and fibroblasts and compound heterozygous mutations in the PDSS2 gene, which encodes a subunit of decaprenyl diphosphate synthase, the first enzyme of the CoQ(10) biosynthetic pathway. Biochemical assays with radiolabeled substrates indicated a severe defect in decaprenyl diphosphate synthase in the patient's fibroblasts. This is the first description of pathogenic mutations in PDSS2 and confirms the molecular and clinical heterogeneity of primary CoQ(10) deficiency.