title: Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome.
abstract: Mevalonic aciduria (MA) and hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) are two autosomal recessive inherited disorders both caused by a deficient activity of the enzyme mevalonate kinase (MK) resulting from mutations in the encoding MVK gene. Thus far, disease-causing mutations only could be detected by analysis of MVK cDNA. We now describe the genomic organization of the human MVK gene. It is 22 kb long and contains 11 exons of 46 to 837 bp and 10 introns of 379 bp to 4.2 kb. Three intron-exon boundaries were confirmed from natural splice variants, indicating the occurrence of exon skipping. Sequence analysis of 27 HIDS and MA patients confirmed all previously reported genotypes based on cDNA analysis and identified six novel nucleotide substitutions resulting in missense or nonsense mutations, providing new insights in the genotype/phenotype relation between HIDS and MA.
authors: Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: S M
authors: SM
authors: Houten
authors: J
authors: J
authors: Koster
authors: G J
authors: GJ
authors: Romeijn
authors: J
authors: J
authors: Frenkel
authors: M
authors: M
authors: Di Rocco
authors: U
authors: U
authors: Caruso
authors: P
authors: P
authors: Landrieu
authors: R I
authors: RI
authors: Kelley
authors: W
authors: W
authors: Kuis
authors: B T
authors: BT
authors: Poll-The
authors: K M
authors: KM
authors: Gibson
authors: R J
authors: RJ
authors: Wanders
authors: H R
authors: HR
authors: Waterham
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D018076:DNA, Complementary; D010505:Familial Mediterranean Fever / Q000201:enzymology* / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D007072:Immunoglobulin D / Q000097:blood*; D008798:Mevalonic Acid / Q000652:urine*; D008969:Molecular Sequence Data; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D012333:RNA, Messenger
chemical_list: D018076:DNA, Complementary; D007072:Immunoglobulin D; D012333:RNA, Messenger; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase; D008798:Mevalonic Acid