Description:
5,10-@METHYLENETETRAHYDROFOLATE REDUCTASE; MTHFR
FACTOR V DEFICIENCY
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
GeT-RM Samples |
| Class |
Disorders of Uncertain Biochemical Etiology |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Relation to Proband
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proband
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Confirmation
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Molecular characterization before cell line submission to CCR
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin confirmed by LINE assay |
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| MUTATION VERIFICATION |
For multiply confirmed mutations by the GeT-RM program please click here: MTHFR SERPINA1 RET BRCA1 and BRCA2 Reference Materials characterized by GeT-RM |
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| Gene |
MTHFR |
| Chromosomal Location |
1p36.3 |
| Allelic Variant 1 |
607093.0003; MTHFR THERMOLABILE POLYMORPHISM |
| Identified Mutation |
677C>T; Frosst et al. [Nature Genet. 10: 111-113 (1995)] identified a C-to-T substitution at nucleotide 677 that converted an alanine to a valine residue. The alteration created a HinfI site that was used to screen 114 unselected French-Canadian chromosomes; the allele frequency of the substitution was 0.38. The mutation in the heterozygous or homozygous state correlated with reduced enzyme activity and increased thermolability in lymphocyte extracts; in vitro expression of the mutagenized cDNA containing the mutation confirmed its effect on thermolability of MTHFR. Individuals homozygous for the mutation had significantly elevated plasma homocysteine levels. Thus, the 677C-T mutation may represent an important genetic risk factor in vascular disease. |
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| Gene |
MTHFR |
| Chromosomal Location |
1p36.3 |
| Allelic Variant 1 |
607093.0004; MTHFR THERMOLABILE POLYMORPHISM |
| Identified Mutation |
1298A>C; Van der Put et al. (1998) identified another polymorphism of the MTHFR gene: a 1298A-C mutation that changed a glutamate into an alanine residue. The mutation destroyed an MboII recognition site and had an allele frequency of 0.33. The 1298A-C mutation resulted in decreased MTHFR activity, which was more pronounced in the homozygous than heterozygous state. Neither the homozygous nor the heterozygous state was associated with higher plasma homocysteine (Hcy) nor a lower plasma folate concentration--phenomena that are evident with homozygosity for the 677C-T mutation (236250.0003). However, combined heterozygosity at the 2 polymorphic sites was associated with reduced MTHFR-specific activity, higher Hcy, and decreased plasma folate levels. Thus, combined heterozygosity for both MTHFR mutations resulted in features similar to those observed in homozygotes for the 677C-T mutation. This combined heterozygosity was observed in 28% of the neural tube defect (NTD) patients compared with 20% among controls, resulting in an odds ratio of 2.04. The data suggested that combined heterozygosity for the 2 common mutations accounts for a proportion of folate-related NTDs, which is not explained by homozygosity for the 677C-T mutation.
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| Gene |
MTHFR |
| Chromosomal Location |
1p36.3 |
| Allelic Variant 2 |
607093.0004; MTHFR THERMOLABILE POLYMORPHISM |
| Identified Mutation |
1298A>C; Van der Put et al. (1998) identified another polymorphism of the MTHFR gene: a 1298A-C mutation that changed a glutamate into an alanine residue. The mutation destroyed an MboII recognition site and had an allele frequency of 0.33. The 1298A-C mutation resulted in decreased MTHFR activity, which was more pronounced in the homozygous than heterozygous state. Neither the homozygous nor the heterozygous state was associated with higher plasma homocysteine (Hcy) nor a lower plasma folate concentration--phenomena that are evident with homozygosity for the 677C-T mutation (236250.0003). However, combined heterozygosity at the 2 polymorphic sites was associated with reduced MTHFR-specific activity, higher Hcy, and decreased plasma folate levels. Thus, combined heterozygosity for both MTHFR mutations resulted in features similar to those observed in homozygotes for the 677C-T mutation. This combined heterozygosity was observed in 28% of the neural tube defect (NTD) patients compared with 20% among controls, resulting in an odds ratio of 2.04. The data suggested that combined heterozygosity for the 2 common mutations accounts for a proportion of folate-related NTDs, which is not explained by homozygosity for the 677C-T mutation.
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| Remarks |
Factor V Leiden heterozygote; negative for Factor II/Prothrombin; donor subject is heterozygous for a C>T mutation at nucleotide 677 in exon 4 of the methylenetetrahydrofolate reductase (MTHFR) gene [677C>T] that results in a substitution of a valine for an alanine at codon 222 [Ala222Val (A222V)] and homozygous for an A>C mutation at nucleotide 1298 (1298A>C) that results in a substitution of an alanine for a glutamic acid at codon 429 [Glu429Ala (E429A)] |
| Barker SD, Bale S, Booker J, Buller A, Das S, Friedman K, Godwin AK, Grody WW, Highsmith E, Kant JA, Lyon E, Mao R, Monaghan KG, Payne DA, Pratt VM, Schrijver I, Shrimpton AE, Spector E, Telatar M, Toji L, Weck K, Zehnbauer B, Kalman LV, Development and characterization of reference materials for MTHFR, SERPINA1, RET, BRCA1, and BRCA2 genetic testing The Journal of molecular diagnostics : JMD11:553-61 2009 |
| PubMed ID: 19767587 |
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