Hansen L L, Brown G K, Kirby D M, Dahl H H
Murdoch Institute for Research into Birth Defects, Royal Children's Hospital, Melbourne, Victoria, Australia.
J Inherit Metab Dis. 1991;14(2):140-51. doi: 10.1007/BF01800586.
The human pyruvate dehydrogenase complex catalyses the oxidative decarboxylation of pyruvate to acetyl-CoA. Defects in several of the seven subunits have been reported, but the majority of mutations affect the E1 component and especially the E1 alpha subunit. However, the clinical presentation of patients with pyruvate dehydrogenase E1 alpha deficiency is extremely variable. Dependency of the brain on pyruvate dehydrogenase activity and localization of the gene for the somatic form of the pyruvate dehydrogenase E1 alpha subunit to the X chromosome provide the basis for a better understanding of the variation in the clinical manifestations. Further understanding of the function and interaction of subunits and the pathophysiology of pyruvate dehydrogenase deficiency necessitates the characterization of mutations in the pyruvate dehydrogenase complex. We report the analysis of three patients with pyruvate dehydrogenase E1 alpha deficiency. One female has a three base pair deletion which affects dephosphorylation of the subunit. Of two males analysed, one has a two base pair deletion causing a shift in the reading frame. The other has a base change, resulting in an Arg to His substitution. All three mutations are located near the carboxyl terminus of the subunit.
人类丙酮酸脱氢酶复合体催化丙酮酸氧化脱羧生成乙酰辅酶A。已报道该复合体七个亚基中的几个存在缺陷，但大多数突变影响E1成分，尤其是E1α亚基。然而，丙酮酸脱氢酶E1α缺乏症患者的临床表现极具变异性。大脑对丙酮酸脱氢酶活性的依赖性以及丙酮酸脱氢酶E1α亚基体细胞形式的基因定位于X染色体，为更好地理解临床表现的变异性提供了基础。进一步了解亚基的功能和相互作用以及丙酮酸脱氢酶缺乏症的病理生理学，需要对丙酮酸脱氢酶复合体中的突变进行表征。我们报告了对三名丙酮酸脱氢酶E1α缺乏症患者的分析。一名女性有一个三碱基对缺失，影响该亚基的去磷酸化。在分析的两名男性中，一名有一个两碱基对缺失，导致阅读框移位。另一名有一个碱基变化，导致精氨酸被组氨酸取代。所有三个突变都位于该亚基的羧基末端附近。
