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Decreased methylene tetrahydrofolate reductase activity due to the 677C→T mutation in families with spina bifida offspring
- Source :
- Journal of Molecular Medicine. 74:691-694
- Publication Year :
- 1996
- Publisher :
- Springer Science and Business Media LLC, 1996.
-
Abstract
- Periconceptional folate intake reduces both the occurrence and recurrence risk of neural tube defects. Plasma homocysteine levels can be elevated in mothers of a child with a neural tube defect, suggesting a dysfunctional folate metabolism. Very recently we showed that a common 677C--T mutation in the 5,10-methylene tetrahydrofolate reductase gene, causing thermolability of the enzyme, is a risk factor for spina bifida offspring. Restriction enzyme analysis of the genomic 5,10-methylene tetrahydrofolate reductase polymerase chain reaction fragment revealed a significantly higher prevalence of a +/+ genotype among spina bifida patients and their mothers. The risk for spina bifida offspring is the strongest if both the mother and her child have the mutation in the homozygous state. Enzymatic analysis showed that homozygosity for the 677C--T mutation causes a decreased 5,10-methylene tetrahydrofolate reductase activity, resulting in elevated plasma homocysteine and red blood cell folate levels and lowered plasma folate and cysteine values. This extended study demonstrates that a nucleotide substitution in the coding region of 5,10-methylene tetrahydrofolate reductase, resulting in reduced activity and an impaired homocysteine and folate metabolism, is a genetic risk factor for spina bifida.
- Subjects :
- Adult
Male
congenital, hereditary, and neonatal diseases and abnormalities
medicine.medical_specialty
5,10-Methylenetetrahydrofolate Reductase (FADH2)
Genotype
Homocysteine
Genetic Linkage
Offspring
Biology
Reductase
medicine.disease_cause
chemistry.chemical_compound
Folic Acid
Risk Factors
Internal medicine
Drug Discovery
medicine
Humans
Point Mutation
Cysteine
Lymphocytes
Child
Spinal Dysraphism
Methylenetetrahydrofolate Reductase (NADPH2)
Genetics (clinical)
Aged
Netherlands
Genetics
Mutation
Neural tube defect
Spina bifida
Homozygote
Neural tube
Middle Aged
medicine.disease
Vitamin B 12
Endocrinology
medicine.anatomical_structure
chemistry
Methylenetetrahydrofolate reductase
biology.protein
Molecular Medicine
Female
Lod Score
Oxidoreductases
Subjects
Details
- ISSN :
- 09462716
- Volume :
- 74
- Database :
- OpenAIRE
- Journal :
- Journal of Molecular Medicine
- Accession number :
- edsair.doi.dedup.....25f0b828745bb0fdec29f113a2fb0d6b