Genetic and non‐genetic factors that increase the risk of non‐syndromic cleft lip and/or palate development

Abstract

Reduced folic acid levels, alcohol consumption, and the MTHFR 677T and 1298C alleles may have contributed to NSCLP development in this sample population from Rio Grande do Norte.

Application of high‐resolution array platform for genome‐wide copy number variation analysis in patients with nonsyndromic cleft lip and palate

“…The mother of one of these patients informed cigarette smoking and alcohol consumption during pregnancy. Clinical data from our study, in agreement with reports in the literature, showed a higher frequency of oral clefts in males, with familial recurrence and an association with environmental risk factors such as maternal exposure to tobacco and alcohol . These results suggest that the presence of microdeletions found in MSX1 may act to potentiate the effects of environmental factors associated with and contributing to the multifactorial etiology of oral clefts.…”

“…The association between candidate genes and environmental factors and their influence on the development of CLP have been widely studied by our group. Specially, the muscle segment homeobox gene 1 ( MSX1) and genes encoding enzymes involved in folate metabolism, such as methionine synthase ( MTR ), methylenetetrahydrofolate reductase ( MTHFR ), and reduced folate carrier 1 ( RFC1 ), have been investigated . Bezerra et al showed a positive association between reduced folic acid levels, alcohol consumption, and the MTHFR 677T and 1298C alleles in NSCLP development .…”

“…Specially, the muscle segment homeobox gene 1 ( MSX1) and genes encoding enzymes involved in folate metabolism, such as methionine synthase ( MTR ), methylenetetrahydrofolate reductase ( MTHFR ), and reduced folate carrier 1 ( RFC1 ), have been investigated . Bezerra et al showed a positive association between reduced folic acid levels, alcohol consumption, and the MTHFR 677T and 1298C alleles in NSCLP development . Cardoso et al found no evidence that the MSX1 polymorphisms rs3775261, rs1042484, rs12532, rs6446693, rs4464513, and rs1907998 play a major role in NSCLP …”

“…Despite advances in identifying genes associated with the NSCLP development using traditional genetic mapping strategies of candidate genes, genomewide studies, animal models, and epidemiologic and linkage analysis, microarray techniques have become important complementary tools in the search for potential causative CLP genes in genetic studies. These techniques allow investigators to scan the whole genome at once and detect submicroscopic chromosomal imbalances called copy number variants (CNVs) .…”

Is MTHFD1 polymorphism rs 2236225 (c.1958G>A) associated with the susceptibility of NSCL/P? A systematic review and meta-analysis

“…Non-syndromic CL/P, accounting for about 70% of CL/P, is considered closely related to genetic and environmental factors 5 . Recent studies suggested that using folic acid could reduce the rates of oral clefts 6, 7 and single nucleotide polymorphisms of some genes such as MTHFR 8, 9 , MTR 40 and MTRR involved in the metabolism of folic acid have been associated to high risk of NSCL/P 8, 9 . Methylenetetrahydrofolate dehydrogenase 1 ( MTHFD1 ), a key gene associated with three sequential enzymatic reactions in the metabolism of folic acid, might play a potential role in the risk of NSCL/P, especially the polymorphism rs2236225 (c.1958G>A) 10 .…”