title: Maternal MTHFR variant forms increase the risk in offspring of isolated nonsyndromic cleft lip with or without cleft palate.
abstract: The pathogenesis of cleft lip with or without cleft palate (CL/P) is complex; its onset could be due to the interaction of various genetic and environmental factors. Recently MTHFR functional polymorphisms were found to increase the risk of this common malformation; however, this finding is still debated. We investigated 110 sporadic CL/P patients, their parents and 289 unrelated controls for c.665C>T (commonly known as 677C>T; p.Ala222Val) and c.1286A>C (known as 1298A>C; p.Glu429Ala) polymorphism in the MTHFR gene. Transmission disequilibrium test (TDT) showed no distortion in allele transmission. Nevertheless, association studies revealed significant differences in allele frequencies between mothers of CL/P patients and controls. This work supports the hypothesis that a lower MTHFR enzyme activity in pregnant women, mostly related to the c.665C>T variant form, is responsible for a higher risk of having CL/P affected offspring.
authors.affiliation: Institute of Histology and General Embryology, University of Bologna, 40126 Bologna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pezzetti
authors.forename: M
authors.initials: M
authors.lastname: Martinelli
authors.forename: L
authors.initials: L
authors.lastname: Scapoli
authors.forename: F
authors.initials: F
authors.lastname: Carinci
authors.forename: A
authors.initials: A
authors.lastname: Palmieri
authors.forename: J
authors.initials: J
authors.lastname: Marchesini
authors.forename: P
authors.initials: P
authors.lastname: Carinci
authors.forename: E
authors.initials: E
authors.lastname: Caramelli
authors.forename: R
authors.initials: R
authors.lastname: Rullo
authors.forename: F
authors.initials: F
authors.lastname: Gombos
authors.forename: M
authors.initials: M
authors.lastname: Tognon
mesh_terms: D032721:Adult Children; D000483:Alleles; D002971:Cleft Lip / Q000453:epidemiology / Q000235:genetics*; D002972:Cleft Palate / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D013577:Syndrome
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)