Malonyl CoA decarboxylase deficiency

C to T transition in intron 2 of the MCD gene

Sankar Surendran, Katherine A. Sacksteder, Stephen J. Gould, James G. Coldwell, Peter L. Rady, Stephan K. Tyring, Reuben Matalon

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Malonyl CoA decarboxylase (MCD) is an enzyme involved in the metabolism of fatty acids synthesis. Based on reports of MCD deficiency, this enzyme is particular important in muscle and brain metabolism. Mutations in the MCD gene result in a deficiency of MCD activity, that lead to psychomotor retardation, cardiomyopathy and neonatal death. To date however, only a few patients have been reported with defects in MCD. We report here studies of a patient with MCD deficiency, who presented with hypotonia, cardiomyopathy and psychomotor retardation. DNA sequencing of MCD revealed a homozygous intronic mutation, specifically a -5 C to T transition near the acceptor site for exon 3. RT-PCR amplification of exons 2 and 3 revealed that although mRNA from a normal control sample yielded one major DNA band, the mutant mRNA sample resulted in two distinct DNA fragments. Sequencing of the patient's two RT-PCR products revealed that the larger molecular weight fragments contained exons 2 and 3 as well as the intervening intronic sequence. The smaller size band from the patient contained the properly spliced exons, similar to the normal control. Western blotting analysis of the expressed protein showed only a faint band in the patient sample in contrast to a robust band in the control. In addition, the enzyme activity of the mutant protein was lower than that of the control protein. The data indicate that homozygous mutation in intron 2 disrupt normal splicing of the gene, leading to lower expression of the MCD protein and MCD deficiency.

Original languageEnglish (US)
Pages (from-to)591-594
Number of pages4
JournalJournal of Neuroscience Research
Volume65
Issue number6
DOIs
StatePublished - Sep 15 2001

Fingerprint

malonyl-CoA decarboxylase
Introns
Exons
Genes
Cardiomyopathies
Mutation
Enzymes
Polymerase Chain Reaction
Messenger RNA
Proteins
Muscle Hypotonia
DNA
Mutant Proteins
DNA Sequence Analysis
Fatty Acids
Molecular Weight
Western Blotting
Malonic aciduria
Muscles
Brain

Keywords

  • Enzyme activity
  • Malonic aciduria
  • MCD
  • Protein expression
  • Splice mutation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Surendran, S., Sacksteder, K. A., Gould, S. J., Coldwell, J. G., Rady, P. L., Tyring, S. K., & Matalon, R. (2001). Malonyl CoA decarboxylase deficiency: C to T transition in intron 2 of the MCD gene. Journal of Neuroscience Research, 65(6), 591-594. https://doi.org/10.1002/jnr.1189

Malonyl CoA decarboxylase deficiency : C to T transition in intron 2 of the MCD gene. / Surendran, Sankar; Sacksteder, Katherine A.; Gould, Stephen J.; Coldwell, James G.; Rady, Peter L.; Tyring, Stephan K.; Matalon, Reuben.

In: Journal of Neuroscience Research, Vol. 65, No. 6, 15.09.2001, p. 591-594.

Research output: Contribution to journalArticle

Surendran, S, Sacksteder, KA, Gould, SJ, Coldwell, JG, Rady, PL, Tyring, SK & Matalon, R 2001, 'Malonyl CoA decarboxylase deficiency: C to T transition in intron 2 of the MCD gene', Journal of Neuroscience Research, vol. 65, no. 6, pp. 591-594. https://doi.org/10.1002/jnr.1189
Surendran S, Sacksteder KA, Gould SJ, Coldwell JG, Rady PL, Tyring SK et al. Malonyl CoA decarboxylase deficiency: C to T transition in intron 2 of the MCD gene. Journal of Neuroscience Research. 2001 Sep 15;65(6):591-594. https://doi.org/10.1002/jnr.1189
Surendran, Sankar ; Sacksteder, Katherine A. ; Gould, Stephen J. ; Coldwell, James G. ; Rady, Peter L. ; Tyring, Stephan K. ; Matalon, Reuben. / Malonyl CoA decarboxylase deficiency : C to T transition in intron 2 of the MCD gene. In: Journal of Neuroscience Research. 2001 ; Vol. 65, No. 6. pp. 591-594.
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