A candidate gene approach to identify modifiers of the palatal phenotype in 22q11.2 deletion syndrome patients

Josine C.C. Widdershoven, Mark Bowser, Molly B. Sheridan, Donna M. McDonald-McGinn, Elaine H. Zackai, Cynthia B. Solot, Richard E. Kirschner, Frits A. Beemer, Bernice E. Morrow, Marcella Devoto, Beverly S. Emanuel

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)123-127
Number of pages5
JournalInternational journal of pediatric otorhinolaryngology
Issue number1
StatePublished - Jan 2013


  • 22q11.2 deletion syndrome
  • Candidate gene
  • Cleft palate

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Otorhinolaryngology


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