title: Two frequent mutations associated with the classic form of propionic acidemia in Taiwan.
abstract: Propionyl-CoA carboxylase (PCC) is involved in the catabolism of branched chain amino acids, odd-numbered fatty acids, cholesterol, and other metabolites. PCC consists of two subunits, α and β, encoded by the PCCA and PCCB genes, respectively. Mutations in the PCCA or PCCB subunit gene may lead to propionic acidemia. In this study, we performed mutation analysis on ten propionic acidemia patients from eight unrelated and nonconsanguineous families in Taiwan. Two PCCA mutations, c.229C→T (p.R77W) and c.1262A→C (p.Q421P), were identified in a PCCA-deficient patient. Six mutations in the PCCB gene, including c.-4156_183+3713del, c.580T→C (p.S194P), c.838dup (p.L280Pfs 11), c.1301C→T (p.A434V), c.1316A→G (P.Y439C), and c.1534C→T (p.R512C), were identified in seven PCCB-deficient families. The c.-4156_183+3713del mutation is the first known large deletion that affects the PCCB gene functions. Furthermore, the c.1301C→T and c.-4156_183+3713del mutations in the PCCB gene have not been reported previously. Clinical features demonstrated that these two frequent mutations are associated with low enzyme activity and a classic propionic acidemia phenotype.
authors.affiliation: Department of Education and Research, Taipei City Hospital, Taipei, Taiwan.
authors.forename: Yen-Hui
authors.initials: YH
authors.lastname: Chiu
authors.forename: Yu-Ning
authors.initials: YN
authors.lastname: Liu
authors.forename: Wei-Ling
authors.initials: WL
authors.lastname: Liao
authors.forename: Ying-Chen
authors.initials: YC
authors.lastname: Chang
authors.forename: Shuan-Pei
authors.initials: SP
authors.lastname: Lin
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Hsu
authors.forename: Pao-Chin
authors.initials: PC
authors.lastname: Chiu
authors.forename: Dau-Ming
authors.initials: DM
authors.lastname: Niu
authors.forename: Chung-Hsing
authors.initials: CH
authors.lastname: Wang
authors.forename: Yu-Yuan
authors.initials: YY
authors.lastname: Ke
authors.forename: Yin-Hsiu
authors.initials: YH
authors.lastname: Chien
authors.forename: Kwang-Jen
authors.initials: KJ
authors.lastname: Hsiao
authors.forename: Tze-Tze
authors.initials: TT
authors.lastname: Liu
mesh_terms: D000483:Alleles; D005260:Female; D056726:Genetic Association Studies; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D043586:Methylmalonyl-CoA Decarboxylase / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D056693:Propionic Acidemia / Q000201:enzymology* / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013624:Taiwan
chemical_list: D021122:Protein Subunits; D043586:Methylmalonyl-CoA Decarboxylase