Genetic characterisation of 22q11.2 variations and prevalence in patients with congenital heart disease
Genetic characterisation of 22q11.2 variations and prevalence in patients with congenital heart disease
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DOI：
10.1136/archdischild-2018-316634
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发表时间：
2020-04-01
影响因子：
5.2
通讯作者：
He, Guo-Wei
中科院分区：
文献类型：
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作者：
Hou, Hai-Tao;Chen, Huan-Xin;He, Guo-Wei
22q11.2缺失综合征被认为是人类最常见的染色体微缺失综合征，也是导致先天性心脏病（CHD）的第二大染色体原因。我们的目的是确定22q11.2区域在包括简单缺陷在内的冠心病儿童中的患病率和详细的遗传特征，并探讨缺失/扩增类型与临床数据之间的基因型-表型关系。方法采用多重结扎探针扩增法和毛细管电泳法对冠心病手术患者进行筛选。应用通用探针库技术进行验证。结果在354例冠心病患者中，40例（11.3%）在22q11.2区域携带不同程度的缺失/扩增，具有不同的表型。该区域的受影响基因包括CDC45（15例）、TBX1（8例）、USP18（8例）、RTDR1（7例）、SNAP29（6例）、TOP3B（6例）、ZNF74（4例）等频率较低的基因。其中，2例患者从CLTCL 1到LZTR I（低拷贝重复A-D）携带3mb典型缺失区域，或从CLTCL 1到MED15（低拷贝重复A-C）携带1.5Mb缺失区域。12例患者出现临床面部表现。本研究揭示了即使在简单缺陷的冠心病患者中，染色体22q11.2变异的发生率也出乎意料地高。基因型表型关系分析表明，22q11.2的基因检测可能在所有冠心病患者中都是必要的，检测独特的缺失或扩增可能为冠心病患者的个性化管理提供有用的见解。
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 CLTCL 1 to LZTR I (low copy repeats A-D) or 1.5Mb deletions from CLTCL 1 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.