title: Genotype and cardiovascular phenotype correlations with TBX1 in 1,022 velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome patients.
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.
authors.affiliation: Department of Genetics, Ob/Gyn and Pediatrics, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Tingwei
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authors.lastname: Guo
authors.forename: Donna
authors.initials: D
authors.lastname: McDonald-McGinn
authors.forename: Anna
authors.initials: A
authors.lastname: Blonska
authors.forename: Alan
authors.initials: A
authors.lastname: Shanske
authors.forename: Anne S
authors.initials: AS
authors.lastname: Bassett
authors.forename: Eva
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authors.lastname: Chow
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authors.forename: Molly
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authors.lastname: Sheridan
authors.forename: Frits
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authors.lastname: Beemer
authors.forename: Koen
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authors.lastname: Devriendt
authors.forename: Ann
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authors.lastname: Swillen
authors.forename: Jeroen
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authors.lastname: Breckpot
authors.forename: Maria C
authors.initials: MC
authors.lastname: Digilio
authors.forename: Bruno
authors.initials: B
authors.lastname: Marino
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Courtney
authors.initials: C
authors.lastname: Carpenter
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.forename: Jacob
authors.initials: J
authors.lastname: Johnson
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chung
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Higgins
authors.forename: Nicole
authors.initials: N
authors.lastname: Philip
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Simon
authors.forename: Karlene
authors.initials: K
authors.lastname: Coleman
authors.forename: Damian
authors.initials: D
authors.lastname: Heine-Suner
authors.forename: Jordi
authors.initials: J
authors.lastname: Rosell
authors.forename: Wendy
authors.initials: W
authors.lastname: Kates
authors.forename: Marcella
authors.initials: M
authors.lastname: Devoto
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Goldmuntz
authors.forename: Elaine
authors.initials: E
authors.lastname: Zackai
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Robert
authors.initials: R
authors.lastname: Shprintzen
authors.forename: Beverly
authors.initials: B
authors.lastname: Emanuel
authors.forename: Bernice
authors.initials: B
authors.lastname: Morrow
mesh_terms: D058165:22q11 Deletion Syndrome / Q000235:genetics*; D018376:Cardiovascular Abnormalities / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004062:DiGeorge Syndrome / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D020825:T-Box Domain Proteins / Q000235:genetics*
chemical_list: D020825:T-Box Domain Proteins; C108625:TBX1 protein, human