Bone Morphogenetic Protein 4 (BMP4) and its association with orofacial clefts
Presentation Category
Research
Introduction/Context/Diagnosis
Bone morphogenetic proteins form a group of growth factors that belong to the transforming growth factor beta superfamily. BMP4 is important regulatory protein that is involved in development of mesoderm, in tooth development, limb formation, induction of bone formation and fracture repair. All members of BMP family have important roles during embryonic development. Disruption in their signaling pathways can adversely affect embryonic development.
Our objective is to review literature related to association of BMP4 gene variants with abnormalities of craniofacial development, specifically non-syndromic cleft lip with or without cleft palate (NSCL/P) anomaly.
Methods/Treatment Plan
Using keywords such as BMP, BMP4, cleft lip and palate, genes and cleft lip and palate in PubMed and Google Scholar search engines, a pertinent literature was obtained. The search was run with no language, ethnicity, or time restrictions. Data from recent research articles and systematic reviews on BMP4 were analyzed and summarized for this presentation. Ten articles and information from five websites were included in this review.
Results/Outcome
Relationships of different BMP4 gene polymorphisms to NSCL/P development were found very different in the reviewed studies. While some studies found that variants at a specific nucleotide led to NSCL/P, other studies had data that showed no association - especially in subsets by ethnicity and by specific types of NSCL/P (cleft lip only, cleft lip and palate, cleft palate only). It was also found that having a specific mutated allele at a certain BMP4 nucleotide increased familial risk for NSCL/P in one population, but exerted a protective effect in another population.
Significance/Conclusions
There is no doubt that BMP genes are among genes that are critically involved in craniofacial development. However, the reviewed studies on association of BMP4 gene variants with NSCL/P did not reveal unequivocal results. Several possible sources of bias might have been involved. Collection methods of case and control samples differed in the compared studies - some were population-based, others were hospital-based. Analyzed case and control samples were relatively small in all studies. Usually, large samples are required to show a significant association of a gene variant with NSCL/P. In addition, etiology of NSCL/P is multifactorial and a proportion of contributing environmental factors often differs.
Future studies should analyze larger samples with bigger sizes of subgroups for ethnicities and types of NSCL/P. Also, analysis of different polymorphisms of the BMP4 gene will help to determine which mutated nucleotide can increase or decrease familial risk for (NSCL/P).
Format
Event
Bone Morphogenetic Protein 4 (BMP4) and its association with orofacial clefts
Bone morphogenetic proteins form a group of growth factors that belong to the transforming growth factor beta superfamily. BMP4 is important regulatory protein that is involved in development of mesoderm, in tooth development, limb formation, induction of bone formation and fracture repair. All members of BMP family have important roles during embryonic development. Disruption in their signaling pathways can adversely affect embryonic development.
Our objective is to review literature related to association of BMP4 gene variants with abnormalities of craniofacial development, specifically non-syndromic cleft lip with or without cleft palate (NSCL/P) anomaly.
