Genetic basis of mitochondrial HMG-CoA synthase deficiency

被引：0

作者：

Rosa Aledo

Johannes Zschocke

Juan Pié

Cecilia Mir

Sonja Fiesel

Ertan Mayatepek

Georg F. Hoffmann

Núria Casals

Fausto G. Hegardt

机构：

[1] Department of Molecular Biology,

[2] International University of Catalonia,undefined

[3] Barcelona,undefined

[4] Spain,undefined

[5] Division of Metabolic and Endocrine Disorders,undefined

[6] University Children´s Hospital,undefined

[7] Heidelberg,undefined

[8] Germany,undefined

[9] Deptartment of Human Genetics,undefined

[10] University of Heidelberg,undefined

[11] Heidelberg,undefined

[12] Germany,undefined

[13] Department of Pharmacology and Physiology,undefined

[14] University of Zaragoza,undefined

[15] Zaragoza,undefined

[16] Spain,undefined

[17] Department of Biochemistry and Molecular Biology,undefined

[18] School of Pharmacy,undefined

[19] University of Barcelona,undefined

[20] Diagonal 643,undefined

[21] E-08028 Barcelona,undefined

[22] Spain,undefined

来源：

Human Genetics | 2001年 / 109卷

关键词：

Methylene Blue; Mevalonate; Serum Free Fatty Acid; Asymmetric Polymerase Chain Reaction; Hypoglycaemic Coma;

D O I：

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学科分类号：

摘要：

Deficiency of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHMGS) is a recessive disorder of ketogenesis that has been previously diagnosed in two children with hypoglycaemic hypoketotic coma during fasting periods. Here, we report the results of molecular investigations in a third patient affected by this disease. Sequencing of the entire coding region of the HMGCS2 gene revealed two missense mutations, G212R and R500H. Mendelian inheritance was confirmed by the analysis of parental samples and neither of the mutations was found on 200 control chromosomes. Functional relevance was confirmed by in vitro expression studies in cytosolic HMGS-deficient cells. Whereas wild-type cDNA of the HMGCS2 gene reverted the auxotrophy for mevalonate, the cDNAs of the mutants did not. The disease may be recognised by specific clinical and biochemical features but it is difficult to confirm enzymatically since the gene is expressed only in liver and testis. Molecular studies may facilitate or confirm future diagnoses in affected patients.

引用

页码：19 / 23

页数：4