Parental origin verification through chromosomal microarray analysis to determine the clinical significance of copy number variations
10.3760/cma.j.cn113903-20200922-00971
- VernacularTitle:染色体微阵列分析技术亲缘分析对判定拷贝数变异临床意义的影响
- Author:
Hairong WU
1
;
Lin LI
;
Yinan MA
;
Chunlian LIU
;
Pei PEI
;
Xuefei ZHENG
;
Songtao WANG
;
Yang XIAO
;
Dingfang BU
;
Yufeng XU
;
Hong PAN
;
Yu QI
Author Information
1. 北京大学第一医院实验中心 100034
- Keywords:
Chromosomes;
Microarray analysis;
DNA copy number variations;
Parents
- From:
Chinese Journal of Perinatal Medicine
2021;24(9):658-664
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the role of parental origin verification in chromosomal microarray analysis (CMA) on the determination of the clinical significance of copy number variations (CNVs).Methods:This retrospective study collected clinical information from 73 core families who underwent prenatal diagnosis at Peking University First Hospital from November 2017 to December 2019. Indications for prenatal diagnosis included ultrasound abnormality in 54 cases (including 12 with thickened nuchal translucency (≥2.5 mm), four with fetal growth restriction, seven with abnormal pregnancy history, and 31 with isolated ultrasound abnormality), NIPT indicated high-risk in four cases, advanced age in nine cases, abnormal pregnancy history alone in three cases, intrauterine death in two cases and one with maternal mental retardation. Genomic DNA of amniotic fluid sample, chorionic villi, cord blood, fetal tissues, and fetal heart blood were extracted using genomic DNA extraction kit. The CNVs of prenatal samples in 73 subjects were analyzed using array-based comparative genomic hybridization (array-CGH) analysis and single nucleotide polymorphism array (SNP-array). Peripheral blood DNA of the couples, and relevant families if necessary, were collected and analyzed in the same way. The results of parental origin detection in CMA were summarized.Results:A total of 76 CNVs were detected in these 73 samples, out of which nine were pathogenic and parental origin detection revealed that six were de novo, two were maternally, and one was paternally inherited; six CNVs were likely pathogenic, including three de novo, two maternally inherited and one paternally inherited; 20 CNVs were variants of uncertain significance, including five paternally inherited, three maternally inherited and 12 de novo; 41 CNVs were likely benign, among which 38 were inherited from parents with normal phenotype. Conclusions:Parental origin verification plays an important role in explaining the clinical significance of detected fetal CNVs and thereby can help to analyze its clinical effect and reproductive risk.
