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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1992 Jan;50(1):229–233.

Identification of a new mutation in medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.

J H Ding 1, B Z Yang 1, Y Bao 1, C R Roe 1, Y T Chen 1
PMCID: PMC1682518  PMID: 1729890

Abstract

A mutation involving an A-to-G nucleotide replacement at position 985 of the medium-chain acyl-CoA dehydrogenase (MCAD) cDNA was found in homozygous form in 18 unrelated MCAD-deficient families and in heterozygous form in 4 families. By PCR amplification and sequencing of cDNA from a compound heterozygote, we have detected a new mutation in an MCAD-deficient patient in whom one MCAD allele produces mRNA that is missing 4 bp in the MCAD cDNA, while the other allele carries the A-to-G-985 mutation. The presence of this 4-bp deletion was confirmed in the patient's genomic DNA by dot-blot hybridization with allele-specific oligonucleotide probes and by restriction analysis of PCR products. A rapid screening test for this 4-bp deletion was developed, based on mismatched primer PCR amplification. The deletion created a new restrictive-enzyme site which yielded two DNA fragments. The 4-bp deletion was not found in the three remaining MCAD chromosomes not harboring the A-to-G-985 mutation, nor it was present in 20 chromosomes from 10 unrelated normal Caucasians. The PCR-based method for screening these two mutations can detect over 93% of all MCAD mutations.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chandley A. C. Asymmetry in chromosome pairing: a major factor in de novo mutation and the production of genetic disease in man. J Med Genet. 1989 Sep;26(9):546–552. doi: 10.1136/jmg.26.9.546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chen Y. T., Negishi M., Nebert D. W. Cytochrome P1-450 structural gene in mouse, rat, and rabbit: differences in DNA methylation and developmental expression of mRNA. DNA. 1982;1(3):231–238. doi: 10.1089/dna.1.1982.1.231. [DOI] [PubMed] [Google Scholar]
  3. Coates P. M., Hale D. E., Stanley C. A., Corkey B. E., Cortner J. A. Genetic deficiency of medium-chain acyl coenzyme A dehydrogenase: studies in cultured skin fibroblasts and peripheral mononuclear leukocytes. Pediatr Res. 1985 Jul;19(7):671–676. doi: 10.1203/00006450-198507000-00007. [DOI] [PubMed] [Google Scholar]
  4. Ding J. H., Roe C. R., Iafolla A. K., Chen Y. T. Medium-chain acyl-coenzyme A dehydrogenase deficiency and sudden infant death. N Engl J Med. 1991 Jul 4;325(1):61–62. doi: 10.1056/NEJM199107043250113. [DOI] [PubMed] [Google Scholar]
  5. Jarman A. P., Wells R. A. Hypervariable minisatellites: recombinators or innocent bystanders? Trends Genet. 1989 Nov;5(11):367–371. doi: 10.1016/0168-9525(89)90171-6. [DOI] [PubMed] [Google Scholar]
  6. Kelly D. P., Kim J. J., Billadello J. J., Hainline B. E., Chu T. W., Strauss A. W. Nucleotide sequence of medium-chain acyl-CoA dehydrogenase mRNA and its expression in enzyme-deficient human tissue. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4068–4072. doi: 10.1073/pnas.84.12.4068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kelly D. P., Whelan A. J., Ogden M. L., Alpers R., Zhang Z. F., Bellus G., Gregersen N., Dorland L., Strauss A. W. Molecular characterization of inherited medium-chain acyl-CoA dehydrogenase deficiency. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9236–9240. doi: 10.1073/pnas.87.23.9236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Matsubara Y., Kraus J. P., Ozasa H., Glassberg R., Finocchiaro G., Ikeda Y., Mole J., Rosenberg L. E., Tanaka K. Molecular cloning and nucleotide sequence of cDNA encoding the entire precursor of rat liver medium chain acyl coenzyme A dehydrogenase. J Biol Chem. 1987 Jul 25;262(21):10104–10108. [PubMed] [Google Scholar]
  9. Matsubara Y., Narisawa K., Miyabayashi S., Tada K., Coates P. M., Bachmann C., Elsas L. J., 2nd, Pollitt R. J., Rhead W. J., Roe C. R. Identification of a common mutation in patients with medium-chain acyl-CoA dehydrogenase deficiency. Biochem Biophys Res Commun. 1990 Aug 31;171(1):498–505. doi: 10.1016/0006-291x(90)91421-n. [DOI] [PubMed] [Google Scholar]
  10. Millington D. S., Norwood D. L., Kodo N., Roe C. R., Inoue F. Application of fast atom bombardment with tandem mass spectrometry and liquid chromatography/mass spectrometry to the analysis of acylcarnitines in human urine, blood, and tissue. Anal Biochem. 1989 Aug 1;180(2):331–339. doi: 10.1016/0003-2697(89)90441-7. [DOI] [PubMed] [Google Scholar]
  11. Mutations in medium chain acyl-CoA dehydrogenase deficiency. Lancet. 1990 Sep 22;336(8717):748–749. [PubMed] [Google Scholar]
  12. Roth D. B., Porter T. N., Wilson J. H. Mechanisms of nonhomologous recombination in mammalian cells. Mol Cell Biol. 1985 Oct;5(10):2599–2607. doi: 10.1128/mcb.5.10.2599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Yokota I., Indo Y., Coates P. M., Tanaka K. Molecular basis of medium chain acyl-coenzyme A dehydrogenase deficiency. An A to G transition at position 985 that causes a lysine-304 to glutamate substitution in the mature protein is the single prevalent mutation. J Clin Invest. 1990 Sep;86(3):1000–1003. doi: 10.1172/JCI114761. [DOI] [PMC free article] [PubMed] [Google Scholar]

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