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

Autor: Kelly, D. P., Hale, D. E., Rutledge, S. L., Ogden, M. L., Whelan, A. J., Zhang, Z., Strauss, A. W.
Zdroj: Journal of Inherited Metabolic Disease; March 1992, Vol. 15 Issue: 2 p171-180, 10p
Abstrakt: 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 thepost mortemidentification of MCAD deficiency.
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