Myoadenylate deaminase deficiency caused by alternative splicing due to a novel intronic mutation in the AMPD1 gene

Paul J. Isackson, Heather Bujnicki, Cary O. Harding, Georgirene D. Vladutiu

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


We have examined two Caucasian brothers with myoadenylate deaminase (AMPD) deficiency who presented with exercise intolerance and muscle cramps. Allele-specific PCR amplification assays demonstrated that the common Q12X (C34T) and P48L (C143T) mutations were not found within their AMPD1 genes. Further analysis revealed that both brothers were compound heterozygotes for a previously reported K287I (A860T) mutation in exon 7 and a novel deletion within intron 2 (IVS2-(4-7)delCTTT). The intronic deletion appears to affect the splicing machinery since characterization of AMPD1 mRNA from skeletal muscle of one brother identified multiple alternatively spliced transcripts resulting in multiple deletions in exon 3, the complete deletion of either exon 3 or exons 3 and 4, and the activation of a cryptic splice site that resulted in an insertion at the 5′ end of exon 4. The predominant transcript contains a 51 base deletion at the 5′ end of exon 3 that is predicted to produce a functional form of AMPD containing a 17-amino acid residue deletion within its N-terminal region. Analysis of 137 Caucasian normal control patients determined that the K287I mutation is relatively frequent (5.1% carrier frequency), whereas the IVS2-(4-7)delCTTT mutation is rare and not present in 274 chromosomes.

Original languageEnglish (US)
Pages (from-to)250-256
Number of pages7
JournalMolecular Genetics and Metabolism
Issue number1-2
StatePublished - Sep 2005


  • Alternative splicing
  • Compound heterozygosity
  • Metabolic myopathy
  • Myoadenylate deaminase deficiency
  • Splice site mutation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology


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