目的 采用全基因组低深度测序技术检测单纯性法洛四联症胎儿中染色体异常，包含染色体非整倍体和拷贝数变异（CNVs），探讨胎儿期单纯性法洛四联症的遗传学特征。方法 收集2014年1月至2017年12月在湖北省妇幼保健院经产前超声会诊及引产后病理检查确诊为单纯性法洛四联症的胎儿24例，利用低深度全基因组测序的方法检测染色体变异，并采用生物信息学方法和美国医学遗传学会及华大基因研究院的解读流程进行CNVs的解读。结果 在24例确诊为单纯性法洛四联症胎儿中，无染色体非整倍体的检出，5例检出有拷贝数变异，其中4例确诊有致病性CNVs（16.7%，4/24）。检出有致病性CNVs的4例胎儿中，3例为DiGeorge综合征，1例为疑似8p inverted duplication/deletion syndrome。结论 胎儿期单纯性法洛四联症与CNVs关系密切，全基因组低覆盖度测序技术可用于发现与单纯性法洛四联症相关的CNVs。
Objective To detect the chromosome anomalies, including whole chromosome aneuploidy and copy number variations (CNVs) from fetuses with isolated tetralogy of Fallot (TOF) by the low-coverage whole-genome sequencing, and explore the genetic characteristics of fetal isolated TOF. Method A total of 24 fetuses with isolated TOF were recruited for this study from January in 2014 to December in 2017 in Maternal and Child Health Hospital of Hubei Province. All of these fetuses had echocardiography at our tertiary referral center, and the diagnosis of isolated TOF was confirmed by pathological examination after induction of labor. The chromosome anomalies was detected by low-coverage whole-genome sequencing and analyzed by bioinformatics tools. Their pathogenicity was interpreted based on the guidelines of the American college of Medical Genetics for sequence variants. Results Of the 24 fetuses confirmed with isolated TOF, no chromosome aneuploidy was detected, and CNVs were identified in 5 fetuses. Pathogenic CNVs were determined in 4 fetuses, accounting for 16.7% of isolated TOF in our case series. These pathogenic CNVs were founded to be associated with known syndromes, including DiGeorge syndrome（3 cases）, and 8p inverted duplication/deletion syndrome (1 case, needed to be confirmed). Conclusions CNVs are likely to be one of the important causes of isolated TOF in fetuses. And the low-coverage whole-genome sequencing technology is a feasible diagnostic technique for fetuses with Isolated TOF.
