Thematic Review Series: Genetics of Human Lipid Diseases Malformation syndromes caused by disorders of cholesterol synthesis
Thematic Review Series: Genetics of Human Lipid Diseases Malformation syndromes caused by disorders of cholesterol synthesis
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发表时间：
2011
影响因子：
3.6
通讯作者：
F. Porter;G. Herman;E. K. Shriver
中科院分区：
文献类型：
--
作者：
F. Porter;G. Herman;E. K. Shriver
胆固醇动态平衡对正常生长发育至关重要。胆固醇除了是一种主要的膜脂外，还具有多种生物学功能。这些作用包括作为合成类固醇激素、神经活性类固醇、氧化类固醇和胆汁酸的前体分子。胆固醇对刺猬蛋白质的正常成熟和信号传递也是必不可少的，因此胆固醇对胚胎发育至关重要。出生后，大多数组织可以从内源性合成或外源性饮食来源获得胆固醇，但在出生前，人类胎儿组织依赖内源性合成。由于血脑屏障，脑组织无法利用饮食或外周产生的胆固醇。一般来说，先天性的胆固醇合成错误既会导致胆固醇的缺乏，也会导致潜在的生物活性或有毒前体类固醇水平的增加。在过去的几十年里，一些人类畸形综合征被证明是由于先天性的胆固醇合成错误所致。在此，我们将对Smith-Lemli-Opitz综合征、结缔组织结构松解症、类固醇松解症、Hem发育不良、X连锁显性点状软骨发育不良、先天性半侧发育不良伴鱼鳞状红皮病和肢体缺陷综合征、类固醇-C-4甲基氧合酶样缺陷和Antley-Bixler综合征的临床和基础科学方面的研究进展作一综述。--波特、F.D.和G.E.赫尔曼。由胆固醇合成障碍引起的畸形综合征。J.Lipid Res。2011年。52：6-34。
Cholesterol homeostasis is critical for normal growth and development. In addition to being a major mem- brane lipid, cholesterol has multiple biological functions. These roles include being a precursor molecule for the syn- thesis of steroid hormones, neuroactive steroids, oxysterols, and bile acids. Cholesterol is also essential for the proper maturation and signaling of hedgehog proteins, and thus cholesterol is critical for embryonic development. After birth, most tissues can obtain cholesterol from either en- dogenous synthesis or exogenous dietary sources, but prior to birth, the human fetal tissues are dependent on endoge- nous synthesis. Due to the blood-brain barrier, brain tissue cannot utilize dietary or peripherally produced cholesterol. Generally, inborn errors of cholesterol synthesis lead to both a defi ciency of cholesterol and increased levels of po- tentially bioactive or toxic precursor sterols. Over the past couple of decades, a number of human malformation syn- dromes have been shown to be due to inborn errors of cho- lesterol synthesis. Herein, we will review clinical and basic science aspects of Smith-Lemli-Opitz syndrome, desmo- sterolosis, lathosterolosis, HEM dysplasia, X-linked domi- nant chondrodysplasia punctata, Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects Syndrome, sterol-C-4 methyloxidase-like defi ciency, and Antley-Bixler syndrome. —Porter, F. D., and G. E. Herman. Malformation syndromes caused by disorders of cholesterol synthesis. J. Lipid Res . 2011. 52: 6-34.