Genetic etiology of fetal conotruncal defects and significance of copy number variation sequencing and whole exome sequencing: analysis of 196 cases
10.3760/cma.j.cn113903-20220926-00852
- VernacularTitle:胎儿圆锥动脉干畸形的遗传学病因及拷贝数变异测序和全外显子组测序在其中的意义：196例分析
- Author:
Xiaoyan HAO
1
;
Tong YI
;
Hairui SUN
;
Ye ZHANG
;
Xiaoyan GU
;
Jiancheng HAN
;
Yihua HE
Author Information
1. 首都医科大学附属北京安贞医院心脏超声医学中心（北京安贞医院胎儿心脏病母胎医学中心），北京 100029
- Keywords:
Heart defects, congenital;
DNA copy number variations;
Whole exome sequencing
- From:
Chinese Journal of Perinatal Medicine
2023;26(4):270-276
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the genetic etiology of fetal conotruncal heart defects (CTDs) and to evaluate the performance of copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) in identifying the genetic etiology.Methods:This retrospective study involved 196 fetuses diagnosed with CTDs by fetal echocardiography in Beijing Anzhen Hospital, Capital Medical University from June 2017 to December 2021. CNV-seq was performed to screen for chromosomal abnormalities [aneuploidy and copy number variations (CNVs)] in the fetuses and their parents, and then WES was performed if CNV-seq was negative. The diagnostic yields of genetic abnormalities [aneuploidy+CNVs+single nucleotide variations (SNVs)] for different types of CTDs were compared using Chi-square test. Results:CNV-seq revealed 54 cases (27.6%, 54/196) with chromosomal abnormalities, including 14 (7.1%, 14/196) aneuploidies, 39 (19.9%, 39/196) CNVs and one aneuploidy complicated by CNVs. Together with another 13 fetuses with pathogenic or likely pathogenic SNVs detected by WES among the rest 142 cases whose CNV-seq results were negative, the total detection rate of genetic abnormalities was 34.2% (67/196). WES increased the diagnostic yield for CTDs by 9.2% (13/142). There was significant difference in the diagnostic yields for different types of CTDs ( χ2=20.31, P=0.002). The diagnostic yield was relatively high for interrupted aortic arch of type B, absent of the pulmonary valve -type of tetralogy of Fallot (9/10 and 8/12), but low for transposition of the great arteries (12.5%, 5/40). Conclusions:CNVs are the common genetic abnormalities in fetal CTDs, and SNVs are also detected in some cases. It is recommended that all fetuses with CTDs should undergo genetic testing. CNV-seq should be used in combination with WES if possible to improve the identification of genetic etiology and provide reference for genetic counseling.
