Two Frequent Mutations Associated with the Classic Form of Propionic Acidemia in Taiwan
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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.
KeywordsPropionic acidemia Propionyl-CoA carboxylase Mutation spectrum Large deletion Taiwan
The work was financially supported by the National Science Council in Taiwan, under grant no. NSC 90-2320-B-010-089, and the Taipei City Government, Taiwan, under grant no. 10101-62-048.
- Fenton WA, Gravel RA, Rosenblatt DS (2001) Disorders of propionate and methylmalonate metabolism. In: Scriver C, Beaudet A, Sly W, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 2165–2190Google Scholar
- Hsu WC, Lin SP, Huang FY, Wang PA, Hsiao KJ (1990) Propionic acidemia: report of a case that is successfully managed by peritoneal dialysis and sodium benzoate therapy. Zhonghua Yi Xue Za Zhi (Taipei) 46:306–310Google Scholar
- Hussein MH, Hashimoto T, Suzuki T, Daoud GA, Goto T, Nakajima Y, Kato T, Hibi M, Tomishige H, Hara F, Kato S, Kakita H, Kamei M, Ito T, Kato I, Sugioka A, Togari H (2013) Children undergoing liver transplantation for treatment of inherited metabolic diseases are prone to higher oxidative stress, complement activity and transforming growth factor-β1. Ann Transplant 18:63–68PubMedCrossRefGoogle Scholar
- Kraus JP, Spector E, Venezia S, Estes P, Chiang PW, Creadon-Swindell G, Müllerleile S, de Silva L, Barth M, Walter M, Walter K, Meissner T, Lindner M, Ensenauer R, Santer R, Bodamer OA, Baumgartner MR, Brunner-Krainz M, Karall D, Haase C, Knerr I, Marquardt T, Hennermann JB, Steinfeld R, Beblo S, Koch HG, Konstantopoulou V, Scholl-Bürgi S, van Teeffelen-Heithoff A, Suormala T, Ugarte M, Sperl W, Superti-Furga A, Schwab KO, Grünert SC, Sass JO (2012) Mutation analysis in 54 propionic acidemia patients. J Inherit Metab Dis 35:51–63PubMedCrossRefGoogle Scholar
- Pérez B, Angaroni C, Sánchez-Alcudia R, Merinero B, Pérez-Cerdá C, Specola N, Rodríguez-Pombo P, Wajner M, de Kremer RD, Cornejo V, Desviat LR, Ugarte M (2010) The molecular landscape of propionic acidemia and methylmalonic aciduria in Latin America. J Inherit Metab Dis 33:S307–S314PubMedCrossRefGoogle Scholar
- Ravn K, Chloupkova M, Christensen E, Brandt NJ, Simonsen H, Kraus JP, Nielsen IM, Skovby F, Schwartz M (2000) High incidence of propionic acidemia in Greenland is due to a prevalent mutation, 1540insCCC, in the gene for the β-subunit of propionyl CoA carboxylase. Am J Hum Genet 67:203–206PubMedCrossRefPubMedCentralGoogle Scholar
- Rodríguez-Pombo P, Hoenicka J, Muro S, Pérez B, Pérez-Cerdá C, Richard E, Desviat LR, Ugarte M (1998) Human propionyl-CoA carboxylase β subunit gene: exon-intron definition and mutation spectrum in Spanish and Latin American propionic acidemia patients. Am J Hum Genet 63:360–369PubMedCrossRefPubMedCentralGoogle Scholar
- Weber JL, Wong C (1993) Mutation of human short tandem repeats. Hum Mol Genet 2:1123–1128Google Scholar
- Yang X, Sakamoto O, Matsubara Y, Kure S, Suzuki Y, Aoki Y, Yamaguchi S, Takahashi Y, Nishikubo T, Kawaguchi C, Yoshioka A, Kimura T, Hayasaka K, Kohno Y, Iinuma K, Ohura T (2004) Mutation spectrum of the PCCA and PCCB genes in Japanese patients with propionic acidemia. Mol Genet Metab 81:335–342PubMedCrossRefGoogle Scholar
- Yorifuji T, Kawai M, Muroi J, Mamada M, Kurokawa K, Shigematsu Y, Hirano S, Sakura N, Yoshida I, Kuhara T, Endo F, Mitsubuchi H, Nakahata T (2002) Unexpectedly high prevalence of the mild form of propionic acidemia in Japan: presence of a common mutation and possible clinical implications. Hum Genet 111:161–165PubMedCrossRefGoogle Scholar