title: Mutation spectrum of the PCCA and PCCB genes in Japanese patients with propionic acidemia.
abstract: Propionic acidemia (PA) is an inborn error of organic acid metabolism caused by a deficiency of propionyl-CoA carboxylase. This enzyme is composed of two non-identical subunits, alpha and beta, which are encoded by the PCCA and PCCB genes, respectively. An enzyme deficiency can result from mutations in either PCCA or PCCB. To elucidate the mutation spectrum in Japanese patients, we have performed a mutation analysis of 30 patients with PA, which included nine previously reported patients. The study revealed that 15 patients were alpha-subunit deficient and 15 patients were beta-subunit deficient. Seven novel mutations were found (IVS18-6C >G, 1746G >A, C398R, G197E and IVS18+1G >A in the PCCA; A153P and IVS9+1G >T in the PCCB). Among these Japanese patients with alpha-subunit deficiencies, 923-924insT, IVS18-6C >G, and R399Q mutations were frequent and the total allelic frequency of these three mutations combined was 56% (17/30). This is in sharp contrast to the mutation spectrum found in Caucasian patients, where no prevalent mutations have been identified. Among the beta-subunit deficiencies, there were three frequent mutations; R410W, T428I, and A153P, whose allelic frequencies were 30, 26.7, and 13.3%, respectively. In conclusion, a limited number of mutations are predominant in both PCCA and PCCB genes among Japanese patients with propionic acidemia.
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.forename: Osamu
authors.initials: O
authors.lastname: Sakamoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsubara
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aoki
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Toshiya
authors.initials: T
authors.lastname: Nishikubo
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kawaguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshioka
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kimura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hayasaka
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kohno
authors.forename: Kazuie
authors.initials: K
authors.lastname: Iinuma
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ohura
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D044466:Asian People; D001483:Base Sequence; D019735:Carbon-Carbon Ligases / Q000235:genetics*; D002460:Cell Line; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019735:Carbon-Carbon Ligases; C022458:propionyl CoA carboxylase (ATP-hydrolyzing)