Wang Huijun, Xiao Feifan, Qian Yanyan, Wu Bingbing, Dong Xinran, Lu Yulan, Cheng Guoqiang, Wang Laishuan, Yan Kai, Yang Lin, Chen Liping, Kang Wenqing, Li Long, Pan Xinnian, Wei Qiufen, Zhuang Deyi, Chen Dongmei, Yin Zhaoqing, Yang Ling, Ni Qi, Liu Renchao, Li Gang, Zhang Ping, Li Xu, Peng Xiaomin, Wang Yao, Chen Huiyao, Ma Xiaojing, Liu Fang, Cao Yun, Huang Guoying, Zhou Wenhao
Center for Molecular Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Division of Neonatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
J Med Genet. 2023 Mar;60(3):247-253. doi: 10.1136/jmedgenet-2021-108354. Epub 2022 May 20.
Congenital heart defects (CHDs) are the most common type of birth defects. The genetic aetiology of CHD is complex and incompletely understood. The overall distribution of genetic causes in patients with CHD from neonatal intensive care units (NICUs) needs to be studied.
CHD cases were extracted from the China Neonatal Genomes Project (2016-2021). Next-generation sequencing results and medical records were retrospectively evaluated to note the frequency of genetic diagnosis and the respective patient outcomes.
In total, 1795 patients were included. The human phenotype ontology term of atrial septal defect, patent ductus arteriosus and ventricular septal defect account for a large portion of the CHD subtype. Co-occurring extracardiac anomalies were observed in 35.1% of patients. 269 of the cases received genetic diagnoses that could explain the phenotype of CHDs, including 172 copy number variations and 97 pathogenic variants. The detection rate of trio-whole-exome sequencing was higher than clinical exome sequencing (21.8% vs 14.5%, p<0.05). Further follow-up analysis showed the genetic diagnostic rate was higher in the deceased group than in the surviving group (29.0% vs 11.9%, p<0.05).
This is the largest cohort study to explore the genetic spectrum of patients with CHD in the NICU in China. Our findings may benefit future work on improving genetic screening and counselling for NICU patients with CHD.
先天性心脏病（CHD）是最常见的出生缺陷类型。CHD的遗传病因复杂，尚未完全明确。需要研究新生儿重症监护病房（NICU）中CHD患者遗传病因的总体分布情况。
从中国新生儿基因组计划（2016 - 2021年）中提取CHD病例。对二代测序结果和病历进行回顾性评估，以记录遗传诊断的频率和相应的患者结局。
共纳入1795例患者。房间隔缺损、动脉导管未闭和室间隔缺损的人类表型本体术语在CHD亚型中占很大一部分。35.1%的患者观察到合并的心外异常。269例病例获得了能够解释CHD表型的遗传诊断，包括172个拷贝数变异和97个致病变异。三联全外显子测序的检出率高于临床外显子测序（21.8%对14.5%，p<0.05）。进一步的随访分析显示，死亡组的遗传诊断率高于存活组（29.0%对11.9%，p<0.05）。
这是中国探索NICU中CHD患者遗传谱的最大队列研究。我们的研究结果可能有助于未来改善NICU中CHD患者的遗传筛查和咨询工作。
