Advertisement

Human Genetics

, Volume 101, Issue 1, pp 93–96 | Cite as

Three novel splice mutations in the PCCA gene causing identical exon skipping in propionic acidemia patients

  • E. Richard
  • Lourdes R. Desviat
  • Belén Pérez
  • Celia Pérez-Cerdá
  • M. Ugarte
Original investigation

Abstract

Propionyl-CoA carboxylase (PCC) is a mitochondrial, biotin-dependent enzyme involved in the catabolism of branched chain amino acids, odd chain fatty acids, and other metabolites. PCC consists of non-identical subunits, α and β, encoded by the PCCA and PCCB genes, respectively. Inherited deficiency of PCC due to mutations in either the PCCA or the PCCB gene results in propionic acidemia (PA), a clinically heterogeneous disorder with a severe, often lethal, neonatal form, and a mild, later onset form. To characterize PCCA gene mutations responsible for PCC deficiency, we analyzed RT-PCR products obtained from cultured fibroblasts from Spanish PCC-α deficient patients. In three patients, smaller than normal PCR products were observed, and sequence analysis revealed the deletion of a 54-bp exon in the cDNA. Sequencing of genomic DNA from these three patients led to the identification of three novel mutations in the PCCA gene, two short deletions and one small insertion, adjacent to short direct repeats, and all of them affecting the consensus splice sites of the skipped exon. These mutations, 1771IVS-2del9, 1824IVS+3del4, and 1824IVS+3insCT, are the cause of the aberrant splicing of the PCCA pre-mRNA and result in an in-frame deletion of 54 nucleotides in the cDNA, probably leading to an unstable protein structure which is responsible for the lack of activity leading to PCC deficiency in these patients.

Keywords

Branch Chain Amino Acid Aberrant Splice Propionic Acidemia Consensus Splice Consensus Splice Site 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • E. Richard
    • 1
  • Lourdes R. Desviat
    • 1
  • Belén Pérez
    • 1
  • Celia Pérez-Cerdá
    • 1
  • M. Ugarte
    • 1
  1. 1.Centro de Biología Molecular “Severo Ochoa”, CSIC-UAM, Facultad de Ciencias, Universidad Autónoma de Madrid, E-28049 Madrid, Spain Tel.: +341-7347011; Fax: +341-7347797 e-mail: mugarte@trasto.cbm.uam.esES

Personalised recommendations