Novel BMP2 Gene 939 SNP is Associated With Cleft Lip/palate Phenotype

Objectives: Genetic factors are the main trigger of cleft lip and palate (CL/P), the most common birth defect. It has been shown in mice that bone morphogenetic protein 2 (BMP2) plays an important role in palatogenesis, but there are no reports on the involvement of BMP2 in the human craniofacial clefts. The aim of this work was to analyze BMP2 gene sequence and describe craniofacial characteristics of CL/P individuals.
Methods: DNA was isolated from 46 CL/P patients and 50 healthy individuals, followed by DNA sequencing of the BMP2 exons. In CL/P individuals bearing the novel SNP 939 were performed 21 measurements on lateral head radiographs and additional familiar and personal data were taken from the medical records to compare with those without the SNP.
Results: Two nucleotide transitions were identified in 929 and 939 position of the BMP2 gene exon 2. The synonymous 929 SNP has been reported previously but unassociated with CLP and was found in 47/50 controls individuals and 37/46 CL/P individuals (p>0,05). The 939 SNP was found in 10 out of 46 CL/P individuals and it was not present in control individuals (p<0,01), defining a significant relationship with the CL/P phenotype. This 939 transition (AàG) change the 91 codon GlyàSer apparently without change the BMP2 conformation. All individuals with 939 SNP had complete CL/P and showed decreased lenght of the skull base, retrognathic maxilla and mandible with a significant size reduction of them. They had predominantly skeletal Class II relationship, anterior facial height increase with vertical growth pattern.
Conclusions: There were found two SNPs in the human BMP2 exon 2. The first one (located at 929 position) had been reported previously but do not related with CL/P. The 939 SNP is a novel one and it was present in the 22% of CL/P individuals and associated with specific craniofacial measurements.