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Genetic characterisation of 22q11.2 variations and prevalence in patients with congenital heart disease
  1. Hai-Tao Hou1,
  2. Huan-Xin Chen1,
  3. Xiu-Li Wang1,
  4. Chao Yuan1,
  5. Qin Yang1,
  6. Zhi-Gang Liu1,
  7. Guo-Wei He1,2,3
  1. 1 Center for Basic Medical Research & Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
  2. 2 Zhejiang University & Wannan Medical College, Hangzhou & Wuhu, China
  3. 3 Department of Surgery, Oregon Health and Science University, Portland, Oregon, United States
  1. Correspondence to Professor Guo-Wei He, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300457, China; gwhezj{at}; Dr Zhi-Gang Liu; liuzg{at}


Objectives The 22q11.2 deletion syndrome is considered the most frequent chromosomal microdeletion syndrome in humans and the second leading chromosomal cause of congenital heart disease (CHD). We aimed to identify the prevalence and the detailed genetic characterisation of 22q11.2 region in children with CHD including simple defects and to explore the genotype-phenotype relationship between deletion/amplification type and clinical data.

Methods Patients with CHD for surgery were screened by multiplex ligation-dependent probe amplification and capillary electrophoresis methods. Universal Probe Library technology was applied for validation.

Results In 354 patients with CHD, 40 (11.3%) carried different levels of deletions/amplifications at the 22q11.2 region with various phenotypes. The affected genes at this region include CDC45 (15 patients), TBX1 (8), USP18 (8), RTDR1 (7), SNAP29 (6), TOP3B (6), ZNF74 (4) and other genes with less frequency. Among those, two patients carried 3 Mb typically deleted region from CLTCL1 to LZTR1 (low copy repeats A–D) or 1.5 Mb deletions from CLTCL1 to MED15 (low copy repeats A–C). Clinical facial manifestations were found in 12 patients.

Conclusions This study revealed an unexpected high prevalence of chromosome 22q11.2 variations in patients with CHD even in simple defects. The genotype-phenotype relationship analysis suggests that genetic detection of 22q11.2 may become necessary in all patients with CHD and that detection of unique deletions or amplifications may provide useful insight into personalised management in patients with CHD.

  • Congenital heart disease
  • Cardiac Surgery

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  • Contributors Conceptualisation: GWH. Data curation: HTH, HXC, XLW, CY, ZGL. Formal analysis: HTH, HXC, GWH. Investigation: HTH, HXC, GWH. Methodology: HTH, HXC, GWH. Supervision: QY, GWH. Visualisation: GWH. Writing (original draft): HTH, GWH. Writing (review and editing): GWH.

  • Funding The work described in this paper was fully supported by grants from the National Natural Science Foundation of China (81870288); the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2019XK310001 & 2018TX31002); the Natural Science Foundation of Zhejiang Province (LY15H020008); the Tianjin Municipal Science and Technology Commission (18PTZWHZ00060); and the Binhai New Area Health Bureau (2016BWKZ003, 2012BWKZ 008).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the Institutional Review Board (Ethics Committee) of TEDA International Cardiovascular Hospital (approval number: [2016]-1219-3). Written Informed consent was obtained from their parents or guardians.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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