title: Role of angiogenesis-related genes in cleft lip/palate: review of the literature.
abstract: OBJECTIVE
  Cleft lip and cleft palate (CLP) are the most common congenital craniofacial anomalies. They have a multifactorial etiology and result from an incomplete fusion of the facial buds. Two main mechanisms, acting alone or interacting with each other, were evidenced in this fusion defect responsible for CLP: defective tissue development and/or defective apoptosis in normal or defective tissues. The objective of this work was to study the implication and role of angiogenesis-related genes in the etiology of CL/P.
  
  
  METHODS
  Our methodological approach included a systematic and thorough analysis of the genes involved in CL/P (syndromic and non-syndromic forms) including previously identified genes but also genes that could potentially be angiogenesis-related (OMIM, Pub Med).We studied the interactions of these different genes and their relationships with potential environmental factors.
  
  
  RESULTS
  TGFβ, FGA, PDGFc, PDGFRa, FGF, FGFR1, FGFR2 growth factors as well as MMP and TIMP2 proteolytic enzymes are involved in the genesis of CLP (P>L). Furthermore, 18 genes involved in CLP also interact with angiogenesis-related genes.
  
  
  CONCLUSIONS
  Even if the main angiogenesis-related genes involved in CLP formation are genes participating in several biological activities and their implication might not be always related to angiogenesis defects, they nevertheless remain an undeniably important research pathway. Furthermore, their interactions with environmental factors make them good candidates in the field of CLP prevention.
authors.affiliation: Department of Pediatric Surgery, American Memorial Hospital, CHU Reims, France; EA 3801 Laboratory Champagne Ardenne University, SFR CAP santé Reims-Amiens, Reims, France; Department of Plastic and Reconstructive Surgery, Hopital Maison Blanche, CHU Reims, France. Electronic address: caro_mtp@hotmail.com.
authors.forename: C
authors.initials: C
authors.lastname: François-Fiquet
authors.affiliation: Department of Pediatric Surgery, American Memorial Hospital, CHU Reims, France.
authors.forename: M L
authors.initials: ML
authors.lastname: Poli-Merol
authors.affiliation: EA 3801 Laboratory Champagne Ardenne University, SFR CAP santé Reims-Amiens, Reims, France.
authors.forename: P
authors.initials: P
authors.lastname: Nguyen
authors.affiliation: Genetics Department, Hôpital Maison Blanche, CHU Reims, France.
authors.forename: E
authors.initials: E
authors.lastname: Landais
authors.affiliation: Genetics Department, Hôpital Maison Blanche, CHU Reims, France.
authors.forename: D
authors.initials: D
authors.lastname: Gaillard
authors.affiliation: EA 3801 Laboratory Champagne Ardenne University, SFR CAP santé Reims-Amiens, Reims, France; Genetics Department, Hôpital Maison Blanche, CHU Reims, France.
authors.forename: M
authors.initials: M
authors.lastname: Doco-Fenzy
mesh_terms: D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D019278:Matrix Metalloproteinase 3
keywords: Angiogenesis; Cleft lip; Cleft palate; Etiologic; Gene; Genetic