Identification and characterization of three novel missense mutations in mevalonate kinase cDNA causing mevalonic aciduria, a disorder of isoprene biosynthesis
Mevalonic aciduria is a rare autosomal recessive metabolic disorder, characterized by psychomotor retardation, failure to thrive, hepatosplenomegaly, anemia and recurrent febrile crises. The disorder is caused by a deficient activity of mevalonate kinase due to mutations in the encoding gene. Thus far, only two disease-causing mutations have been identified. We now report four different missense mutations including three novel ones, which were identified by sequence analysis of mevalonate kinase cDNA from three mevalonic aciduria patients. All mutations affect conserved amino acids. Heterologous expression of the corresponding mutant mevalonate kinases as fusion proteins with glutathione S -transferase in Escherichia coli showed a profound effect of each of the mutations on enzyme activity. In addition, immunoblot analysis of fibroblast lysates from patients using specific antibodies against mevalonate kinase identified virtually no protein. These results demonstrate that the mutations affect not only the activity but also the stability of the mutant proteins.
Mevalonate kinase assay using DEAE-cellulose column chromatography for first-trimester prenatal diagnosis and complementation analysis in mevalonic aciduria
Molecular analysis of the yeast VPS3 gene and the role of its product in vacuolar protein sorting and vacuolar segregation during the cell cycle
A patient with mevalonic aciduria presenting with hepatosplenomegaly, congenital anaemia, thrombocytopenia and leukocytosis
Electroblotting of multiple gels: a simple apparatus without buffer tank for rapid transfer of proteins from polyacrylamide to nitrocellulose
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Cholesterol biosynthesis in Zellweger syndrome: normal activity of mevalonate kinase, mevalonate-5'-pyrophosphate decarboxylase and IPP-isomerase in patients' fibroblasts but deficient mevalonate kinase activity in liver
Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata
Rhizomelic chondrodysplasia punctata is a peroxisomal protein targeting disease caused by a non-functional PTS2 receptor
Rhizomelic chondrodysplasia punctata is caused by deficiency of human PEX7, a homologue of the yeast PTS2 receptor
Identification of an active site alanine in mevalonate kinase through characterization of a novel mutation in mevalonate kinase deficiency.
Differential deficiency of mevalonate kinase and phosphomevalonate kinase in patients with distinct defects in peroxisome biogenesis: evidence for a major role of peroxisomes in cholesterol biosynthesis
Characterization of mevalonate kinase V377I, a mutant implicated in defective isoprenoid biosynthesis and HIDS/periodic fever syndrome
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Liver transplantation followed by allogeneic hematopoietic stem cell transplantation for atypical mevalonic aciduria
Mevalonate kinase deficiency associated with ataxia and retinitis pigmentosa in two brothers with MVK gene mutations
MVK gene abnormality and new approach to treatment of hyper IgD syndrome and periodic fever syndrome
Carrier frequency of the V377I (1129G>A) MVK mutation, associated with Hyper-IgD and periodic fever syndrome, in the Netherlands
MVK mutations and associated clinical features in Italian patients affected with autoinflammatory disorders and recurrent fever
Pseudodominant inheritance of the hyperimmunoglobulinemia D with periodic fever syndrome in a mother and her two monozygotic twins
Molecular modeling and simulation study of homoserine kinase as an effective leishmanial drug target.
The structure of a binary complex between a mammalian mevalonate kinase and ATP: insights into the reaction mechanism and human inherited disease
Regulation of isoprenoid/cholesterol biosynthesis in cells from mevalonate kinase-deficient patients.
Statin-induced proinflammatory response in mitogen-activated peripheral blood mononuclear cells through the activation of caspase-1 and IL-18 secretion in monocytes
Molecular basis of classical mevalonic aciduria and the hyperimmunoglobulinaemia D and periodic fever syndrome: high frequency of 3 mutations in the mevalonate kinase gene
Phenotypic diversity, disease progression, and pathogenicity of MVK missense variants in mevalonic aciduria.
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