title: Genomic and mutational analysis of the mitochondrial trifunctional protein beta-subunit (HADHB) gene in patients with trifunctional protein deficiency.
abstract: Mitochondrial trifunctional protein (TP), an enzyme of beta-oxidation, is a multienzyme complex composed of four molecules of the alpha-subunit (HADHA) containing the enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase domains and four molecules of the beta-subunit (HADHB) containing the 3-ketoacyl-CoA thiolase domain. An inborn error of this enzyme complex can cause sudden infant death syndrome, acute hepatic encephalopathy or liver failure, skeletal myopathy, or hypertrophic cardiomyopathy. TP deficiency is classified into two different biochemical phenotypes: one represents the existence of both subunits and the lack of only the 3-hydroxyacyl-CoA dehydrogenase activity and the other represents the absence of both subunits and the lack of all three TP activities, although their clinical features are similar. We have identified two Japanese patients with this disorder. Three enzyme activities of TP were undetectable in fibroblasts from these two patients. We detected two mutations in the HADHB gene from two Japanese patients, an exonic single T insertion which created a new cryptic 5' splice site and a G1331A transition (R411 K). Patient 1 was a compound heterozygote, while patient 2 was a homozygote of a G1331A transition.
authors.affiliation: Department of Pediatrics, Gifu University School of Medicine, Tsukasa-machi, Japan. kenjior-gif@umin.u-tokyo.ac.jp
authors.forename: K E
authors.initials: KE
authors.lastname: Orii
authors.forename: T
authors.initials: T
authors.lastname: Aoyama
authors.forename: K
authors.initials: K
authors.lastname: Wakui
authors.forename: Y
authors.initials: Y
authors.lastname: Fukushima
authors.forename: H
authors.initials: H
authors.lastname: Miyajima
authors.forename: S
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Orii
authors.forename: N
authors.initials: N
authors.lastname: Kondo
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002874:Chromosome Mapping; D006224:Cricetinae; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D015870:Gene Expression; D006801:Humans; D063991:Mitochondrial Trifunctional Protein; D063992:Mitochondrial Trifunctional Protein, alpha Subunit; D063993:Mitochondrial Trifunctional Protein, beta Subunit; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000172:deficiency* / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D009097:Multienzyme Complexes; C576205:HADHA protein, human; D063992:Mitochondrial Trifunctional Protein, alpha Subunit; C576206:HADHB protein, human; D063991:Mitochondrial Trifunctional Protein; D063993:Mitochondrial Trifunctional Protein, beta Subunit