title: A candidate gene approach to identify modifiers of the palatal phenotype in 22q11.2 deletion syndrome patients.
abstract: OBJECTIVE
  Palatal anomalies are one of the identifying features of 22q11.2 deletion syndrome (22q11.2DS) affecting about one third of patients. To identify genetic variants that increase the risk of cleft or palatal anomalies in 22q11.2DS patients, we performed a candidate gene association study in 101 patients with 22q11.2DS genotyped with the Affymetrix genome-wide human SNP array 6.0.
  
  
  METHODS
  Patients from Children's Hospital of Philadelphia, USA and Wilhelmina Children's Hospital Utrecht, The Netherlands were stratified based on palatal phenotype (overt cleft, submucosal cleft, bifid uvula). SNPs in 21 candidate genes for cleft palate were analyzed for genotype-phenotype association. In addition, TBX1 sequencing was carried out. Quality control and association analyses were conducted using the software package PLINK.
  
  
  RESULTS
  Genotype and phenotype data of 101 unrelated patients (63 non-cleft subjects (62.4%), 38 cleft subjects (37.6%)) were analyzed. A Total of 39 SNPs on 10 genes demonstrated a p-value ≤0.05 prior to correction. The most significant SNPs were found on FGF10. However none of the SNPs remained significant after correcting for multiple testing.
  
  
  CONCLUSIONS
  Although these results are promising, analysis of additional samples will be required to confirm that variants in these regions influence risk for cleft palate or palatal anomalies in 22q11.2DS patients.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Maastricht University Medical Center, The Netherlands. josine.widdershoven@mumc.nl
authors.forename: Josine C C
authors.initials: JC
authors.lastname: Widdershoven
authors.forename: Mark
authors.initials: M
authors.lastname: Bowser
authors.forename: Molly B
authors.initials: MB
authors.lastname: Sheridan
authors.forename: Donna M
authors.initials: DM
authors.lastname: McDonald-McGinn
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
authors.forename: Cynthia B
authors.initials: CB
authors.lastname: Solot
authors.forename: Richard E
authors.initials: RE
authors.lastname: Kirschner
authors.forename: Frits A
authors.initials: FA
authors.lastname: Beemer
authors.forename: Bernice E
authors.initials: BE
authors.lastname: Morrow
authors.forename: Marcella
authors.initials: M
authors.lastname: Devoto
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Emanuel
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis*; D002892:Chromosomes, Human, Pair 22; D002972:Cleft Palate / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D004062:DiGeorge Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005838:Genotype; D006776:Hospitals, Pediatric; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D010641:Phenotype; D012494:Sampling Studies; D014481:United States / Q000453:epidemiology