Document Type
Peer-Reviewed Article
Publication Date
11-2011
Abstract
Haploinsufficiency of TBX1, encoding a T-box transcription factor, is largely responsible for the physical malformations in velo-cardio-facial /DiGeorge/22q11.2 deletion syndrome (22q11DS) patients. Cardiovascular malformations in these patients are highly variable, raising the question as to whether DNA variations in the TBX1 locus on the remaining allele of 22q11.2 could be responsible. To test this, a large sample size is needed. The TBX1 gene was sequenced in 360 consecutive 22q11DS patients. Rare and common variations were identified. We did not detect enrichment in rare SNP (single nucleotide polymorphism) number in those with or without a congenital heart defect. One exception was that there was increased number of very rare SNPs between those with normal heart anatomy compared to those with right-sided aortic arch or persistent truncus arteriosus, suggesting potentially protective roles in the SNPs for these phenotype-enrichment groups. Nine common SNPs (minor allele frequency, MAF > 0.05) were chosen and used to genotype the entire cohort of 1,022 22q11DS subjects. We did not find a correlation between common SNPs or haplotypes and cardiovascular phenotype. This work demonstrates that common DNA variations in TBX1 do not explain variable cardiovascular expression in 22q11DS patients, implicating existence of modifiers in other genes on 22q11.2 or elsewhere in the genome.
DOI
10.1002/humu.21568
PMID
21796729
Recommended Citation
Guo,Tingwei, et al. "Genotype and Cardiovascular Phenotype Correlations With TBX1 in 1,022 Velo-Cardio-Facial/Digeorge/22q11.2 Deletion Syndrome Patients." Human Mutation 32.11 (2011): 1278-1289.
Publication
Human Mutation
Volume
32
Issue
11
Publisher
Wiley
Pages
1278-1289
Included in
Communication Sciences and Disorders Commons, Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons
Comments
Version posted is the NIH Public Access Author Manuscript.
At the time of publication Robert Shprintzen was affiliated with Velo-Cardio-Facial Syndrome International Center, Department of Otolaryngology and Communication Science, SUNY Upstate Medical University, Syracuse, NY.