Molecular basis of inherited medium-chain acyl-CoA dehydrogenase deficiency causing sudden child death

D. P. Kelly, D. E. Hale, S. L. Rutledge, M. L. Ogden, A. J. Whelan, Z. Zhang, A. W. Strauss

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47 Scopus citations


Deficiency of medium-chain acyl-CoA dehydrogenase (MCAD) is an important cause of sudden death in children. The majority of surviving individuals with MCAD deficiency studied to date are homozygous for a single point mutation at bp 985 of the MCAD mRNA (A985G). We have now identified a four-base-pair deletion in exon 11 of one allele of the MCAD gene in an American child who died of MCAD deficiency. The deletion mutation results in a frameshift and premature termination codon in the mutant MCAD mRNA. The second mutant allele contained the common point mutation A985G, and thus the proband was a compound heterozygote. Protein immunoblot analysis of the child's liver proteins revealed that the mutant MCAD proteins were barely detectable. Allele-specific oligonucleotide hybridization analysis performed on amplified exon 11 of the child's MCAD gene clearly identified both mutations. MCAD RFLP analysis of the patient's DNA revealed heterozygosity at the Taq I MCAD RFLP site, thus, the two mutations are associated with different haplotypes. Therefore, we have identified a new mutation in the MCAD gene and have developed a nucleic-acid-based screening approach which allows the post mortem identification of MCAD deficiency.

Original languageEnglish (US)
Pages (from-to)171-180
Number of pages10
JournalJournal of Inherited Metabolic Disease
Issue number2
StatePublished - Mar 1992

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


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