title: Detecting 22q11.2 deletion in Chinese children with conotruncal heart defects and single nucleotide polymorphisms in the haploid TBX1 locus.
abstract: BACKGROUND
  Conotruncal heart defects (CTDs) are present in 75-85% of patients suffering from the 22q11.2 deletion syndrome. To date, no consistent phenotype has been consistently correlated with the 22q11.2 deletions. Genetic studies have implicated TBX1 as a critical gene in the pathogenesis of the syndrome. The aim of study was to determine the incidence of the 22q11.2 deletion in Chinese patients with CTDs and the possible mechanism for pathogenesis of CTDs.
  
  
  METHODS
  We enrolled 212 patients with CTDs and 139 unrelated healthy controls. Both karyotypic analysis and multiplex ligation-dependent probe amplification were performed for all CTDs patients. Fluorescence in situ hybridization was performed for the patients with genetic deletions and their relatives. The TBX1 gene was sequenced for all patients and healthy controls. The χ2 and Fisher's exact test were used in the statistical analysis.
  
  
  RESULTS
  Thirteen of the 212 patients with CTDs (6.13%) were found to have the 22q11.2 deletion syndrome. Of the 13 cases, 11 presented with a hemizygous interstitial microdeletion from CLTCL1 to LZTR1; one presented with a regional deletion from CLTCL1 to DRCR8; and one presented with a regional deletion from CDC45L to LZTR1. There were eight sequence variants in the haploid TBX1 genes of the del22q11 CTDs patients. The frequency of one single nucleotide polymorphism (SNP) in the del22q11 patients was different from that of the non-del patients (P < 0.05), and the frequencies of two other SNPs were different between the non-del CTDs patients and controls (P < 0.05).
  
  
  CONCLUSIONS
  CTDs, especially pulmonary atresia with ventricular septal defect and tetralogy of Fallot, are the most common disorders associated with the 22q11.2 deletion syndrome. Those patients with both CTDs and 22q11.2 deletion generally have a typical or atypical deletion region within the TBX1 gene. Our results indicate that TBX1 genetic variants may be associated with CTDs.
authors.affiliation: Department of Pediatric Cardiology, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.
authors.forename: Yue-Juan
authors.initials: YJ
authors.lastname: Xu
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Rang
authors.initials: R
authors.lastname: Xu
authors.forename: Peng-Jun
authors.initials: PJ
authors.lastname: Zhao
authors.forename: Xi-Ke
authors.initials: XK
authors.lastname: Wang
authors.forename: Heng-Juan
authors.initials: HJ
authors.lastname: Sun
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Bao
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Qi-Hua
authors.initials: QH
authors.lastname: Fu
authors.forename: Fen
authors.initials: F
authors.lastname: Li
authors.forename: Kun
authors.initials: K
authors.lastname: Sun
mesh_terms: D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D020732:Cytogenetic Analysis; D004062:DiGeorge Syndrome / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D006238:Haploidy; D006330:Heart Defects, Congenital / Q000150:complications / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D020825:T-Box Domain Proteins / Q000032:analysis / Q000235:genetics*
chemical_list: D020825:T-Box Domain Proteins; C108625:TBX1 protein, human