Shi Panlai, Xia Yanjie, Li Qianqian, Kong Xiangdong
Genetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
J Obstet Gynaecol Res. 2021 Mar;47(3):1002-1008. doi: 10.1111/jog.14627. Epub 2021 Jan 20.
Families with an adverse history of monogenic disease focus on single-gene diagnosis instead of low-depth whole-genome sequence, during subsequent pregnancies. The aim of this study was to assess the potential usefulness of low-depth whole-genome sequencing (copy number variant sequencing [CNV-seq]) detection following monogenic disease exclusion in prenatal diagnosis.
A total of 285 families with a history of monogenic disease (of 41 different types; eliminated during the current pregnancy) were recruited and retrospectively analyzed. Low-depth whole-genome sequencing (CNV-Seq, Next-Seq CN500 platform) was performed for all fetuses.
The CNV detection results of the 285 samples were as follows: one case of 18-trisomy chimera (0.35%), one case of pathogenic 3q29 microdeletion syndrome CNV (0.35%), four cases of variant of uncertain significance (VUS) CNVs (1.40%), and four cases of Duchenne muscular dystrophy (DMD) carriers (1.40%); and the remaining samples were normal (96.15%). Of note, 2/285 (0.70%) samples still exhibited pathogenic abnormalities. All positive samples were followed up where the two cases of pathogenic abnormalities elected the pregnancy termination, while the four VUS cases and four DMD-carrier cases were born healthy.
In cases where prenatal fetal monogenic disease has been ruled out, CNV detection is still beneficial and should be performed to prevent missed pathogenic CNVs. However, the costs need to be balanced against benefits, and the research will need to assess other types of testing.
有单基因疾病不良病史的家庭在后续妊娠期间关注的是单基因诊断而非低深度全基因组测序。本研究的目的是评估在产前诊断中排除单基因疾病后进行低深度全基因组测序（拷贝数变异测序[CNV-seq]）检测的潜在效用。
招募了285个有单基因疾病病史（41种不同类型；在本次妊娠期间已排除）的家庭并进行回顾性分析。对所有胎儿进行低深度全基因组测序（CNV-Seq，Next-Seq CN500平台）。
285个样本的CNV检测结果如下：1例18-三体嵌合体（0.35%），1例致病性3q29微缺失综合征CNV（0.35%），4例意义未明变异（VUS）CNV（1.40%），以及4例杜氏肌营养不良（DMD）携带者（1.40%）；其余样本均正常（96.15%）。值得注意的是，2/285（0.70%）的样本仍表现出致病性异常。所有阳性样本均进行了随访，其中2例致病性异常样本选择了终止妊娠，而4例VUS病例和4例DMD携带者病例出生后健康。
在产前胎儿单基因疾病已被排除的情况下，CNV检测仍然有益，应进行检测以防止遗漏致病性CNV。然而，需要在成本和效益之间进行权衡，并且该研究还需要评估其他类型的检测。
