title: Nucleotide sequence of messenger RNA encoding human isovaleryl-coenzyme A dehydrogenase and its expression in isovaleric acidemia fibroblasts.
abstract: Isovaleric acidemia (IVA) is caused by a genetic deficiency of isovaleryl-CoA dehydrogenase (IVD). At least five distinct variant IVD alleles are known. We isolated five overlapping IVD cDNA clones from a human placenta cDNA library. They covered the entire coding region, except the initiation codon, and 587 bp in the 3'-noncoding region plus the poly(A) tail. The structure of the initiation site was identified by the study of genomic DNA and by the sequence comparison with rat IVD. Human IVD shared 89.6, 35.8, and 31.6% identical amino acid residues with rat IVD and human short and medium chain acyl-CoA dehydrogenases, respectively. In the Northern blot analysis of normal human liver and fibroblast poly(A)+ RNA, three mRNA species of different sizes (4.6, 3.8, and 2.1 kb) hybridized to IVD cDNA. Three mRNA species with similar sizes were also detected in five IVA fibroblast lines of different genotypes (variants 1, 1 X 2, 2, 3, and 5), suggesting that these variants are each due to a point mutation or small deletion.
authors.affiliation: Department of Human Genetics, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: Y
authors.initials: Y
authors.lastname: Matsubara
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: R
authors.initials: R
authors.lastname: Glassberg
authors.forename: S
authors.initials: S
authors.lastname: Satyabhama
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000302:isolation & purification; D044943:Fatty Acid Desaturases / Q000235:genetics; D005347:Fibroblasts / Q000032:analysis; D045782:Hemiterpenes; D006801:Humans; D050769:Isovaleryl-CoA Dehydrogenase; D008969:Molecular Sequence Data; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010421:Pentanoic Acids / Q000097:blood*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D014631:Valerates / Q000097:blood*
chemical_list: D045782:Hemiterpenes; D010421:Pentanoic Acids; D012333:RNA, Messenger; D014631:Valerates; C008216:isovaleric acid; D004247:DNA; D010088:Oxidoreductases; D044943:Fatty Acid Desaturases; D044925:Oxidoreductases Acting on CH-CH Group Donors; D050769:Isovaleryl-CoA Dehydrogenase