TY - JOUR
T1 - A candidate gene approach to identify modifiers of the palatal phenotype in 22q11.2 deletion syndrome patients
AU - Widdershoven, Josine C.C.
AU - Bowser, Mark
AU - Sheridan, Molly B.
AU - McDonald-McGinn, Donna M.
AU - Zackai, Elaine H.
AU - Solot, Cynthia B.
AU - Kirschner, Richard E.
AU - Beemer, Frits A.
AU - Morrow, Bernice E.
AU - Devoto, Marcella
AU - Emanuel, Beverly S.
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
KW - 22q11.2 deletion syndrome
KW - Candidate gene
KW - Cleft palate
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U2 - 10.1016/j.ijporl.2012.10.009
DO - 10.1016/j.ijporl.2012.10.009
M3 - Article
C2 - 23121717
AN - SCOPUS:84871490395
SN - 0165-5876
VL - 77
SP - 123
EP - 127
JO - International journal of pediatric otorhinolaryngology
JF - International journal of pediatric otorhinolaryngology
IS - 1
ER -