Evaluation of potential modifiers of the palatal phenotype in the 22q11.2 deletion syndrome.
OBJECTIVE
To evaluate potential modifiers of the palatal phenotype in individuals with the 22q11.2 deletion syndrome.


METHODS
Data from 356 subjects enrolled in a study of the 22q11.2 deletion syndrome were used to evaluate potential modifiers of the palatal phenotype. Specifically, subjects with and without velopharyngeal inadequacy and/or structural malformations of the palate were compared with respect to gender, race, and genotype for variants of seven genes that may influence palatal development.


METHODS
The chi-square test or Fisher exact test was used to evaluate the association between palatal phenotype and each potential modifier. Odds ratios and their associated 95% confidence intervals were used to measure the magnitude of the association between palatal phenotype, subject gender and race, and each of the bi-allelic variants.


RESULTS
The palatal phenotype observed in individuals with the 22q11.2 deletion syndrome was significantly associated with both gender and race. In addition, there was tentative evidence that the palatal phenotype may be influenced by variation within the gene that encodes methionine synthase.


CONCLUSIONS
Variation in the palatal phenotype observed between individuals with the 22q11.2 deletion syndrome may be related to personal characteristics such as gender and race as well as variation within genes that reside outside of the 22q11.2 region.
Driscoll
Deborah A
DA
Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, USA.
Boland
Torrey
T
Emanuel
Beverly S
BS
Kirschner
Richard E
RE
LaRossa
Don
D
Manson
Jeanne
J
McDonald-McGinn
Donna
D
Randall
Peter
P
Solot
Cynthia
C
Zackai
Elaine
E
Mitchell
Laura E
LE
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000096:biosynthesis; D016009:Chi-Square Distribution; D002648:Child; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000201:enzymology / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D002972:Cleft Palate / Q000150:complications*; D003541:Cystathionine beta-Synthase / Q000096:biosynthesis; D005006:Ethnicity; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000096:biosynthesis; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000096:biosynthesis; D021362:Palate, Hard / Q000002:abnormalities*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D013577:Syndrome; D014681:Velopharyngeal Insufficiency / Q000209:etiology / Q000235:genetics*
C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D003541:Cystathionine beta-Synthase