Cystathionine beta-synthase c.844ins68 gene variant and non-syndromic cleft lip and palate.
Non-syndromic cleft lip with or without cleft palate (CL/P) is a common birth defect with substantial clinical and social impact and whose causes include both genetic and environmental factors. Folate and homocysteine (Hcy) metabolism have been indicated to play a role in the etiology of CL/P, and polymorphisms in folate and Hcy genes may act as susceptibility factors. We investigated a common polymorphism in the cystathionine beta-synthase (CBS) gene (c.844ins68) in 134 Italian CL/P cases and their parents using the transmission disequilibrium test (TDT). Although no overall linkage disequilibrium was observed, considering the parent-of-origin transmission of the CBS 68 bp insertion a significant (P = 0.002) transmission distortion was detected. When children receive the c.844ins68 allele from the mother compared to the father, they show a 18.7-fold increase in risk for CL/P. This evidence suggests CBS as a candidate gene for CL/P and supports a role of maternal-embryo interactions in the etiology of CL/P.
Rubini
Michele
M
Department of Experimental and Diagnostic Medicine, Medical Genetics Unit, University of Ferrara, Ferrara, Italy. rub@unife.it
Brusati
Roberto
R
Garattini
Giovanna
G
Magnani
Cinzia
C
Liviero
Fabio
F
Bianchi
Fabrizio
F
Tarantino
Enrico
E
Massei
Alessandro
A
Pollastri
Susanna
S
Carturan
Sabrina
S
Amadori
Alice
A
Bertagnin
Elisa
E
Cavallaro
Alessandra
A
Fabiano
Anna
A
Franchella
Andrea
A
Calzolari
Elisa
E
D000483:Alleles; D002971:Cleft Lip / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D002972:Cleft Palate / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium; D008297:Male; D009679:Nuclear Family; D011110:Polymorphism, Genetic
D003541:Cystathionine beta-Synthase