Title: Overt cleft palate phenotype and TBX1 genotype correlations in velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome patients
Authors: Herman, Sean B ×
Guo, Tingwei
McGinn, Donna M McDonald
Blonska, Anna
Shanske, Alan L
Bassett, Anne S
Chow, Eva W C
Bowser, Mark
Sheridan, Molly
Beemer, Frits
Devriendt, Koenraad
Swillen, Ann
Breckpot, Jeroen
Digilio, M Cristina
Marino, Bruno
Dallapiccola, Bruno
Carpenter, Courtney
Zheng, Xin
Johnson, Jacob
Chung, Jonathan
Higgins, Anne Marie
Philip, Nicole
Simon, Tony
Coleman, Karlene
Heine-Suner, Damian
Rosell, Jordi
Kates, Wendy
Devoto, Marcella
Zackai, Elaine
Wang, Tao
Shprintzen, Robert
Emanuel, Beverly S
Morrow, Bernice E
and the International Chromosome 22q11.2 Consortium #
Issue Date: Nov-2012
Publisher: Wiley-Liss
Series Title: American Journal of Medical Genetics A vol:158A issue:11 pages:2781-2787
Article number: 10.1002/ajmg.a.35512
Abstract: Velo-cardio-facial syndrome/DiGeorge syndrome, also known as 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome, with an estimated incidence of 1/2,000-1/4,000 live births. Approximately 9-11% of patients with this disorder have an overt cleft palate (CP), but the genetic factors responsible for CP in the 22q11DS subset are unknown. The TBX1 gene, a member of the T-box transcription factor gene family, lies within the 22q11.2 region that is hemizygous in patients with 22q11DS. Inactivation of one allele of Tbx1 in the mouse does not result in CP, but inactivation of both alleles does. Based on these data, we hypothesized that DNA variants in the remaining allele of TBX1 may confer risk to CP in patients with 22q11DS. To test the hypothesis, we evaluated TBX1 exon sequencing (n = 360) and genotyping data (n = 737) with respect to presence (n = 54) or absence (n = 683) of CP in patients with 22q11DS. Two upstream SNPs (rs4819835 and rs5748410) showed individual evidence for association but they were not significant after correction for multiple testing. Associations were not identified between DNA variants and haplotypes in 22q11DS patients with CP. Overall, this study indicates that common DNA variants in TBX1 may be nominally causative for CP in patients with 22q11DS. This raises the possibility that genes elsewhere on the remaining allele of 22q11.2 or in the genome could be relevant. © 2012 Wiley Periodicals, Inc.
ISSN: 1552-4825
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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