A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy
A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy
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DOI：
10.1086/512130
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发表时间：
2007-03-01
影响因子：
9.8
通讯作者：
Marquardt, Thorsten
中科院分区：
文献类型：
--
作者：
Kranz, Christian;Jungeblut, Christoph;Marquardt, Thorsten
下面的研究描述了一种新的遗传性代谢紊乱，多醇激酶（DK1）缺乏症的发现。DK1负责磷酸多醇从头合成的最后一步。磷酸二醇参与多种糖基化反应，如n -糖基化、糖基磷脂酰肌醇（GPI）锚定生物合成以及c -和o -甘露糖基化。我们发现了四名患者，他们在相应的hDK1基因中具有两种突变（C . 295t -> A[99Cys -> Ser]或C . 1322a -> C [441Tyr -> Ser]）中的一种纯合。与对照细胞相比，突变体DK1的剩余活性为2%-4%。突变的等位基因不能弥补dk1缺陷酵母细胞的温度敏感表型，而野生型等位基因恢复了正常生长表型。受影响的患者表现出非常严重的临床表型，在婴儿期早期死亡。2例患者死于扩张性心肌病。
The following study describes the discovery of a new inherited metabolic disorder, dolichol kinase (DK1) deficiency. DK1 is responsible for the final step of the de novo biosynthesis of dolichol phosphate. Dolichol phosphate is involved in several glycosylation reactions, such as N-glycosylation, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, and C-and O-mannosylation. We identified four patients who were homozygous for one of two mutations (c.295T -> A[99Cys -> Ser] or c.1322A -> C [441Tyr -> Ser]) in the corresponding hDK1 gene. The residual activity of mutant DK1 was 2%-4% when compared with control cells. The mutated alleles failed to complement the temperature-sensitive phenotype of DK1-deficient yeast cells, whereas the wild-type allele restored the normal growth phenotype. Affected patients present with a very severe clinical phenotype, with death in early infancy. Two of the patients died from dilative cardiomyopathy.