Molecular basis for methionine synthase reductase deficiency in patients belonging to the cblE complementation group of disorders in folatecobalamin metabolism.
Molecular basis for methionine synthase reductase deficiency in patients belonging to the cblE complementation group of disorders in folatecobalamin metabolism.
Clinical onset and course, response to treatment and outcome in 24 patients with the cblE or cblG remethylation defect complemented by genetic and in vitro enzyme study data.
Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFR 677C-->T, MTRR 66A-->G and the relationship between these genotypes and the risk of Down syndrome was analyzed.
With the purpose of evaluating this relationship, we compared the frequencies of 677C>T and 1298A>C polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and 66A>G in the methionine synthase reductase gene (MTRR) between 103 young mothers of Down syndrome (DS) individuals and 108 control mothers, whose offspring was karyotypically normal, correlating it with an estimative of folate and - related micronutrients levels intake.
Overall, we found that maternal MTHFR C677T polymorphism (OR(TvsC) =1.20; 95% CI = 1.13-1.28) and MTRR A66G polymorphism (OR(GvsA) = 1.21; 95% CI = 0.98-1.49) were risk factors for producing offspring with NTD but maternal MTHFR A1298C polymorphism (OR(CvsA) = 0.91; 95% CI = 0.78-1.07) was not associated with NTD risk.
To investigate the role of four parental folate pathway single nucleotide polymorphisms (SNPs) i.e., methylene tetrahydrofolate reductase (MTHFR) 677C>T, MTHFR 1298A>C, methionine synthase reductase (MTRR) 66A>G and glutamate carboxypeptidase (GCP) II 1561C>T on susceptibility to neural tube defects (NTDs) in 50 couples with NTD offspring and 80 couples with normal pregnancy outcome.
The methionine-synthase-reductase A66G, the methionine-synthase A2756G and the cystathionine-beta-synthase 844ins68 polymorphisms were not associated with increased risk of Down syndrome.
Contradictory findings have been recently published on the evaluation of genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR 677 C-->T) and methionine synthase reductase (MTRR 66 A-->G) as risk factors for having a child with Down syndrome (DS); however, the influence of polymorphisms of methionine synthase (MTR 2756 A-->G) and of MTHFR 1298 A-->C has never been evaluated.
In conclusion, MTRR A66G is significantly more common in mothers of children with Down syndrome but does not appear to increase the risk for Down syndrome by changing homocysteine metabolism.
The present meta-analysis indicated that MTRR A66G polymorphism, but not MTR A2756G, is significantly associated with maternal risk for NTDs in Caucasians.
This study aimed to analyze a dataset of genetic and cytogenetic data in an Italian group of MDS and mothers of healthy children (control mothers) to assess the predictive capacity of artificial neural networks assembled in TWIST system in distinguish consistently these two different conditions and to identify the variables expressing the maximal amount of relevant information to the condition of being mother of a DS child.The dataset consisted of the following variables: the frequency of chromosome damage in peripheral lymphocytes (BNMN frequency) and the genotype for 7 common polymorphisms in folate metabolic genes (MTHFR 677C>T and 1298A>C, MTRR 66A>G, MTR 2756A>G, RFC1 80G>A and TYMS 28bp repeats and 1494 6bp deletion).
The MTHFR 677C-->T polymorphism was shown to represent a risk factor in NTD cases (CC v CT+TT odds ratio (OR) 2.03 [95% confidence interval (CI) 1.09, 3.79] p = 0.025) and the MTRR 66A-->G</span> polymorphism was shown to exert a protective effect in NTD cases (AA v AG+GG OR 0.31 [95% CI 0.10, 0.94] p = 0.04).