Molecular survey of a prevalent mutation, 985A-to-G transition, and identification of five infrequent mutations in the medium-chain acyl-CoA dehydrogenase (MCAD) gene in 55 patients with MCAD deficiency

I. Yokota, P. M. Coates, D. E. Hale, P. Rinaldo, K. Tanaka

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Abstract

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an inborn error of fatty-acid oxidation that is characterized by fasting intolerance and recurrent episodes of hypoglycemic coma which can be fatal. Its incidence is one of the highest among genetic metabolic disorders. Using a modified PCR and NcoI digestion method, we have surveyed 46 additional, unrelated MCAD- deficient patients for a prevalent mutation, an 985A-to-G transition (985A→G), that we previously identified in nine MCAD-deficient patients. Among the total of 55 studied, 44 were homozygous and 10 were heterozygous for the 985G allele, whereas one did not carry this mutant allele, indicating that the prevalence of the 985G allele is 89.1%. Furthermore, we identified five other types of mutation: one each in three of the compound heterozygotes and two in the single non-985G patient. An RFLP study of 12 985G-homozygotes showed that all 24 alleles fell into a single haplotype. A questionnaire regarding the ethnic and national origin of their patients was sent to all referring investigators. All 41 patients for whom this information was provided were Caucasians. Of 29 patients whose country of origin was specified, 19 and five were from the British Isles and Germany, respectively. These data suggest that 985A→G may have occurred in a single person in an ancient Germanic tribe.

Original languageEnglish (US)
Pages (from-to)1280-1291
Number of pages12
JournalAmerican Journal of Human Genetics
Volume49
Issue number6
StatePublished - Dec 1 1991

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Acyl-CoA Dehydrogenase
Mutation
Alleles
Genes
Inborn Genetic Diseases
Homozygote
Heterozygote
Coma
Population Groups
Hypoglycemic Agents
Restriction Fragment Length Polymorphisms
Haplotypes
Germany
Medium chain acyl CoA dehydrogenase deficiency
Surveys and Questionnaires
Digestion
Fasting
Fatty Acids
Research Personnel
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

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title = "Molecular survey of a prevalent mutation, 985A-to-G transition, and identification of five infrequent mutations in the medium-chain acyl-CoA dehydrogenase (MCAD) gene in 55 patients with MCAD deficiency",
abstract = "Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an inborn error of fatty-acid oxidation that is characterized by fasting intolerance and recurrent episodes of hypoglycemic coma which can be fatal. Its incidence is one of the highest among genetic metabolic disorders. Using a modified PCR and NcoI digestion method, we have surveyed 46 additional, unrelated MCAD- deficient patients for a prevalent mutation, an 985A-to-G transition (985A→G), that we previously identified in nine MCAD-deficient patients. Among the total of 55 studied, 44 were homozygous and 10 were heterozygous for the 985G allele, whereas one did not carry this mutant allele, indicating that the prevalence of the 985G allele is 89.1{\%}. Furthermore, we identified five other types of mutation: one each in three of the compound heterozygotes and two in the single non-985G patient. An RFLP study of 12 985G-homozygotes showed that all 24 alleles fell into a single haplotype. A questionnaire regarding the ethnic and national origin of their patients was sent to all referring investigators. All 41 patients for whom this information was provided were Caucasians. Of 29 patients whose country of origin was specified, 19 and five were from the British Isles and Germany, respectively. These data suggest that 985A→G may have occurred in a single person in an ancient Germanic tribe.",
author = "I. Yokota and Coates, {P. M.} and Hale, {D. E.} and P. Rinaldo and K. Tanaka",
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T1 - Molecular survey of a prevalent mutation, 985A-to-G transition, and identification of five infrequent mutations in the medium-chain acyl-CoA dehydrogenase (MCAD) gene in 55 patients with MCAD deficiency

AU - Yokota, I.

AU - Coates, P. M.

AU - Hale, D. E.

AU - Rinaldo, P.

AU - Tanaka, K.

PY - 1991/12/1

Y1 - 1991/12/1

N2 - Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an inborn error of fatty-acid oxidation that is characterized by fasting intolerance and recurrent episodes of hypoglycemic coma which can be fatal. Its incidence is one of the highest among genetic metabolic disorders. Using a modified PCR and NcoI digestion method, we have surveyed 46 additional, unrelated MCAD- deficient patients for a prevalent mutation, an 985A-to-G transition (985A→G), that we previously identified in nine MCAD-deficient patients. Among the total of 55 studied, 44 were homozygous and 10 were heterozygous for the 985G allele, whereas one did not carry this mutant allele, indicating that the prevalence of the 985G allele is 89.1%. Furthermore, we identified five other types of mutation: one each in three of the compound heterozygotes and two in the single non-985G patient. An RFLP study of 12 985G-homozygotes showed that all 24 alleles fell into a single haplotype. A questionnaire regarding the ethnic and national origin of their patients was sent to all referring investigators. All 41 patients for whom this information was provided were Caucasians. Of 29 patients whose country of origin was specified, 19 and five were from the British Isles and Germany, respectively. These data suggest that 985A→G may have occurred in a single person in an ancient Germanic tribe.

AB - Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an inborn error of fatty-acid oxidation that is characterized by fasting intolerance and recurrent episodes of hypoglycemic coma which can be fatal. Its incidence is one of the highest among genetic metabolic disorders. Using a modified PCR and NcoI digestion method, we have surveyed 46 additional, unrelated MCAD- deficient patients for a prevalent mutation, an 985A-to-G transition (985A→G), that we previously identified in nine MCAD-deficient patients. Among the total of 55 studied, 44 were homozygous and 10 were heterozygous for the 985G allele, whereas one did not carry this mutant allele, indicating that the prevalence of the 985G allele is 89.1%. Furthermore, we identified five other types of mutation: one each in three of the compound heterozygotes and two in the single non-985G patient. An RFLP study of 12 985G-homozygotes showed that all 24 alleles fell into a single haplotype. A questionnaire regarding the ethnic and national origin of their patients was sent to all referring investigators. All 41 patients for whom this information was provided were Caucasians. Of 29 patients whose country of origin was specified, 19 and five were from the British Isles and Germany, respectively. These data suggest that 985A→G may have occurred in a single person in an ancient Germanic tribe.

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