How to Cite this Article: Herman SB, Guo T, McDonald McGinn DM, Blonska A, Shanske AL, Bassett AS, Chow EWC, Bowser M, Sheridan M, Beemer F, Devriendt K, Swillen A, Breckpot J, Digilio MC, Marino B, Dallapiccola B, Carpenter C, Zheng X, Johnson J, Chung J, Higgins AM, Philip N, Simon T, Coleman K, Heine-Suner D, Rosell J, Kates W, Devoto M, Zackai E, Wang T, Shprintzen R, Emanuel BS, Morrow BE, and the International Chromosome 22q11.2 Consortium. 2012. Overt cleft palate phenotype and TBX1 genotype correlations in velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome patients. Am J Med Genet Part A 158A: 2781–2787.
Overt cleft palate phenotype and TBX1 genotype correlations in velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome patients†
Article first published online: 3 OCT 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Special Issue: SPECIAL ISSUE: GROWTH CHARTS IN GENETIC SYNDROMES
Volume 158A, Issue 11, pages 2781–2787, November 2012
How to Cite
Herman, S. B., Guo, T., McGinn, D. M. M., Blonska, A., Shanske, A. L., Bassett, A. S., Chow, E. W.C., Bowser, M., Sheridan, M., Beemer, F., Devriendt, K., Swillen, A., Breckpot, J., Digilio, M. C., Marino, B., Dallapiccola, B., Carpenter, C., Zheng, X., Johnson, J., Chung, J., Higgins, A. M., Philip, N., Simon, T., Coleman, K., Heine-Suner, D., Rosell, J., Kates, W., Devoto, M., Zackai, E., Wang, T., Shprintzen, R., Emanuel, B. S., Morrow, B. E. and and the International Chromosome 22q11.2 Consortium (2012), Overt cleft palate phenotype and TBX1 genotype correlations in velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome patients. Am. J. Med. Genet., 158A: 2781–2787. doi: 10.1002/ajmg.a.35512
- Issue published online: 17 OCT 2012
- Article first published online: 3 OCT 2012
- Manuscript Accepted: 16 MAY 2012
- Manuscript Received: 27 DEC 2011
- NIH. Grant Numbers: HL084410, P01HD070454
- The Charles E.H. Upham Chair (BSE)
- 22q11.2 deletion syndrome;
- TBX1 sequencing;
- cleft palate;
- genomic disorder
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.