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Two Frequent Mutations Associated with the Classic Form of Propionic Acidemia in Taiwan

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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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Education and Research, Taipei City Hospital, Taipei, Taiwan

    Yen-Hui Chiu, Kwang-Jen Hsiao & Tze-Tze Liu

  2. Institute of Genetics, National Yang-Ming University, Taipei, Taiwan

    Yen-Hui Chiu, Yu-Ning Liu & Wei-Ling Liao

  3. VYM Genome Research Center, National Yang-Ming University, No. 155, Sec. 2, Li-Nong Street, Beitou, Taipei, 11221, Taiwan

    Ying-Chen Chang & Tze-Tze Liu

  4. Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan

    Shuan-Pei Lin

  5. Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Chia-Chi Hsu & Pao-Chin Chiu

  6. Section of Genetics and Metabolism, Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan

    Chia-Chi Hsu & Yu-Yuan Ke

  7. Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

    Pao-Chin Chiu

  8. Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan

    Dau-Ming Niu

  9. Department of Pediatrics, Children’s Hospital, China Medical University and Hospitals, Taichung, Taiwan

    Chung-Hsing Wang

  10. Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan

    Yin-Hsiu Chien

  11. Preventive Medicine Foundation, Taipei, Taiwan

    Kwang-Jen Hsiao

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  1. Yen-Hui Chiu
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Correspondence to Tze-Tze Liu.

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Chiu, YH., Liu, YN., Liao, WL. et al. Two Frequent Mutations Associated with the Classic Form of Propionic Acidemia in Taiwan. Biochem Genet 52, 415–429 (2014). https://doi.org/10.1007/s10528-014-9657-6

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  • DOI: https://doi.org/10.1007/s10528-014-9657-6

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