Mutation analysis in 54 propionic acidemia patients

J. P. Kraus, E. Spector, S. Venezia, P. Estes, Pei-Wen Chiang, G. Creadon-Swindell, S. Müllerleile, L. De Silva, M. Barth, M. Walter, K. Walter, T. Meissner, M. Lindner, R. Ensenauer, R. Santer, O. A. Bodamer, M. R. Baumgartner, M. Brunner-Krainz, D. Karall, C. HaaseI. Knerr, T. Marquardt, J. B. Hennermann, R. Steinfeld, S. Beblo, H. G. Koch, V. Konstantopoulou, S. Scholl-Bürgi, A. Van Teeffelen-Heithoff, T. Suormala, M. Ugarte, W. Sperl, A. Superti-Furga, K. O. Schwab, S. C. Grünert, J. O. Sass

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Deficiency of propionyl CoA carboxylase (PCC), a dodecamer of alpha and beta subunits, causes inherited propionic acidemia. We have studied, at the molecular level, PCC in 54 patients from 48 families comprised of 96 independent alleles. These patients of various ethnic backgrounds came from research centers and hospitals in Germany, Austria and Switzerland. The thorough clinical characterization of these patients was described in the accompanying paper (Grünert et al. 2012). In all 54 patients, many of whom originated from consanguineous families, the entire PCCB gene was examined by genomic DNA sequencing and in 39 individuals the PCCA gene was also studied. In three patients we found mutations in both PCC genes. In addition, in many patients RT-PCR analysis of lymphoblast RNA, lymphoblast enzyme assays, and expression of new mutations in E.coli were carried out. Eight new and eight previously detected mutations were identified in the PCCA gene while 15 new and 13 previously detected mutations were found in the PCCB gene. One missense mutation, p.V288I in the PCCB gene, when expressed in E.coli, yielded 134% of control activity and was consequently classified as a polymorphism in the coding region. Numerous new intronic polymorphisms in both PCC genes were identified. This study adds a considerable amount of new molecular data to the studies of this disease.

Original languageEnglish (US)
Pages (from-to)51-63
Number of pages13
JournalJournal of Inherited Metabolic Disease
Volume35
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

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Propionic Acidemia
Methylmalonyl-CoA Decarboxylase
Mutation
Genes
Escherichia coli
Austria
Enzyme Assays
Missense Mutation
Switzerland
DNA Sequence Analysis
Germany
Alleles
RNA
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Kraus, J. P., Spector, E., Venezia, S., Estes, P., Chiang, P-W., Creadon-Swindell, G., ... Sass, J. O. (2012). Mutation analysis in 54 propionic acidemia patients. Journal of Inherited Metabolic Disease, 35(1), 51-63. https://doi.org/10.1007/s10545-011-9399-0

Mutation analysis in 54 propionic acidemia patients. / Kraus, J. P.; Spector, E.; Venezia, S.; Estes, P.; Chiang, Pei-Wen; Creadon-Swindell, G.; Müllerleile, S.; De Silva, L.; Barth, M.; Walter, M.; Walter, K.; Meissner, T.; Lindner, M.; Ensenauer, R.; Santer, R.; Bodamer, O. A.; Baumgartner, M. R.; Brunner-Krainz, M.; Karall, D.; Haase, C.; Knerr, I.; Marquardt, T.; Hennermann, J. B.; Steinfeld, R.; Beblo, S.; Koch, H. G.; Konstantopoulou, V.; Scholl-Bürgi, S.; Van Teeffelen-Heithoff, A.; Suormala, T.; Ugarte, M.; Sperl, W.; Superti-Furga, A.; Schwab, K. O.; Grünert, S. C.; Sass, J. O.

In: Journal of Inherited Metabolic Disease, Vol. 35, No. 1, 01.2012, p. 51-63.

Research output: Contribution to journalArticle

Kraus, JP, Spector, E, Venezia, S, Estes, P, Chiang, P-W, 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', Journal of Inherited Metabolic Disease, vol. 35, no. 1, pp. 51-63. https://doi.org/10.1007/s10545-011-9399-0
Kraus JP, Spector E, Venezia S, Estes P, Chiang P-W, Creadon-Swindell G et al. Mutation analysis in 54 propionic acidemia patients. Journal of Inherited Metabolic Disease. 2012 Jan;35(1):51-63. https://doi.org/10.1007/s10545-011-9399-0
Kraus, J. P. ; Spector, E. ; Venezia, S. ; Estes, P. ; Chiang, Pei-Wen ; Creadon-Swindell, G. ; Müllerleile, S. ; De Silva, L. ; Barth, M. ; Walter, M. ; Walter, K. ; Meissner, T. ; Lindner, M. ; Ensenauer, R. ; Santer, R. ; Bodamer, O. A. ; Baumgartner, M. R. ; Brunner-Krainz, M. ; Karall, D. ; Haase, C. ; Knerr, I. ; Marquardt, T. ; Hennermann, J. B. ; Steinfeld, R. ; Beblo, S. ; Koch, H. G. ; Konstantopoulou, V. ; Scholl-Bürgi, S. ; Van Teeffelen-Heithoff, A. ; Suormala, T. ; Ugarte, M. ; Sperl, W. ; Superti-Furga, A. ; Schwab, K. O. ; Grünert, S. C. ; Sass, J. O. / Mutation analysis in 54 propionic acidemia patients. In: Journal of Inherited Metabolic Disease. 2012 ; Vol. 35, No. 1. pp. 51-63.
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abstract = "Deficiency of propionyl CoA carboxylase (PCC), a dodecamer of alpha and beta subunits, causes inherited propionic acidemia. We have studied, at the molecular level, PCC in 54 patients from 48 families comprised of 96 independent alleles. These patients of various ethnic backgrounds came from research centers and hospitals in Germany, Austria and Switzerland. The thorough clinical characterization of these patients was described in the accompanying paper (Gr{\"u}nert et al. 2012). In all 54 patients, many of whom originated from consanguineous families, the entire PCCB gene was examined by genomic DNA sequencing and in 39 individuals the PCCA gene was also studied. In three patients we found mutations in both PCC genes. In addition, in many patients RT-PCR analysis of lymphoblast RNA, lymphoblast enzyme assays, and expression of new mutations in E.coli were carried out. Eight new and eight previously detected mutations were identified in the PCCA gene while 15 new and 13 previously detected mutations were found in the PCCB gene. One missense mutation, p.V288I in the PCCB gene, when expressed in E.coli, yielded 134{\%} of control activity and was consequently classified as a polymorphism in the coding region. Numerous new intronic polymorphisms in both PCC genes were identified. This study adds a considerable amount of new molecular data to the studies of this disease.",
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AU - Spector, E.

AU - Venezia, S.

AU - Estes, P.

AU - Chiang, Pei-Wen

AU - Creadon-Swindell, G.

AU - Müllerleile, S.

AU - De Silva, L.

AU - Barth, M.

AU - Walter, M.

AU - Walter, K.

AU - Meissner, T.

AU - Lindner, M.

AU - Ensenauer, R.

AU - Santer, R.

AU - Bodamer, O. A.

AU - Baumgartner, M. R.

AU - Brunner-Krainz, M.

AU - Karall, D.

AU - Haase, C.

AU - Knerr, I.

AU - Marquardt, T.

AU - Hennermann, J. B.

AU - Steinfeld, R.

AU - Beblo, S.

AU - Koch, H. G.

AU - Konstantopoulou, V.

AU - Scholl-Bürgi, S.

AU - Van Teeffelen-Heithoff, A.

AU - Suormala, T.

AU - Ugarte, M.

AU - Sperl, W.

AU - Superti-Furga, A.

AU - Schwab, K. O.

AU - Grünert, S. C.

AU - Sass, J. O.

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