Cleft Lip and Palate and MSX1 CA-Repeats Polymorphism

Cleft lip and palate is the most common craniofacial congenital abnormality, occurring in one of every 500 to 1000 births. In developing countries, the incidence is on the highest side. Though the exact etiology of cleft lip and palate is uncertain, some candidate genes, such as TGFA, TGFB3, MTHFR, and MSX1, have a role in its development.

OBJECTIVES: A pilot case-control study was performed to evaluate a possible association between maternal MSX1 CA repeat polymorphism and nonsyndromic cleft lip and palate (NCLP) in a Guatemalan population.

METHODS: DNA was isolated from dry blood spots on filter paper collected during Rotaplast medical missions to Guatemala. Segments of DNA containing the CA repeats were amplified using PCR, purified, and sequenced. The sequences were read in a graphical format and genotypes consisting of alleles 1-4 were established. Allele 1 had 12 CA repeats, allele 2 had 11 CA repeats, allele 3 had 10 CA repeats, and allele 4 had 9 CA repeats.

RESULTS: Our sample consisted of 140 mothers of patients affected with NCLP (case mothers) and 52 mothers of unaffected children (control mothers). The most common genotype was A4A4. A higher proportion of A4A4 homozygotes were seen among the case mothers (58.58%) than among the control mothers (46.16%). The A4 allele was present in 75% of the case mothers and in 66% of the control mothers.

CONCLUSIONS: Our findings complemented our studies carried out previously that showed a higher frequency of the A4 allele among both those affected by NCLP and their parents, especially the mothers. Although the differences we found between the case and control mothers were not statistically significant, we did show a higher frequency of the A4A4 genotype and of the A4 allele in mothers of children affected with NCLP than in mothers of healthy children.