Maternal MTHFR variant forms increase the risk in offspring of isolated nonsyndromic cleft lip with or without cleft palate.
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.
Pezzetti
F
F
Institute of Histology and General Embryology, University of Bologna, 40126 Bologna, Italy.
Martinelli
M
M
Scapoli
L
L
Carinci
F
F
Palmieri
A
A
Marchesini
J
J
Carinci
P
P
Caramelli
E
E
Rullo
R
R
Gombos
F
F
Tognon
M
M
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
D042965:Methylenetetrahydrofolate Reductase (NADPH2)