title: Evidence for a structural mutation (347Ala to Thr) in a German family with 3-ketothiolase deficiency.
abstract: The molecular basis of 3-ketothiolase deficiency (3KTD) was examined in a 3KTD family. Immunochemical analyses showed that mitochondrial acetoacetyl-CoA thiolase (T2) biosynthesized in the patient's fibroblasts (GK06) was unstable and that the parents and brother were obligatory carriers of 3KTD. When sequencing the PCR-amplified patient's T2 cDNA, we noted a G to A replacement which caused 347Ala to Thr substitution of the mature T2 subunit. Transfection analysis revealed that this substitution resulted in an instability of the T2 protein. Analyses of the T2 cDNA and gene of the family indicated that the patient was a compound heterozygote; the allele that derived from the mother had a point mutation (347Ala to Thr) and the other allele from the father has a mutation which would abolish the T2 gene expression. This report is apparently the first definition of a mutant allele for 3KTD, at the gene level.
authors.affiliation: Department of Pediatrics, Gifu University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fukao
authors.forename: S
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: S
authors.initials: S
authors.lastname: Tomatsu
authors.forename: T
authors.initials: T
authors.lastname: Orii
authors.forename: G
authors.initials: G
authors.lastname: Frauendienst-Egger
authors.forename: L
authors.initials: L
authors.lastname: Schrod
authors.forename: T
authors.initials: T
authors.lastname: Osumi
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D000102:Acetyl-CoA C-Acyltransferase / Q000172:deficiency / Q000235:genetics*; D000409:Alanine; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002648:Child; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D015183:Restriction Mapping; D013912:Threonine
chemical_list: D015345:Oligonucleotide Probes; D013912:Threonine; D012313:RNA; D000102:Acetyl-CoA C-Acyltransferase; D000409:Alanine