Premium
Maternal MTHFR variant forms increase the risk in offspring of isolated nonsyndromic cleft lip with or without cleft palate
Author(s) -
Pezzetti F.,
Martinelli M.,
Scapoli L.,
Carinci F.,
Palmieri A.,
Marchesini J.,
Carinci P.,
Caramelli E.,
Rullo R.,
Gombos F.,
Tog M.
Publication year - 2004
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9257
Subject(s) - methylenetetrahydrofolate reductase , transmission disequilibrium test , offspring , allele , biology , genetics , polymorphism (computer science) , pathogenesis , allele frequency , linkage disequilibrium , risk factor , pregnancy , medicine , haplotype , gene , immunology
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. © 2004 Wiley‐Liss, Inc.