Influence of validating the parental origin on the clinical interpretation of fetal copy number variations in 141 core family cases
Abstract Background The sources and variants types of the copy number variations (CNVs) in prenatal fetal, and the critical role of parental origin on the interpretation of fetal CNVs are unclear. Methods One hundred and forty‐one prenatal core families with abnormal CNVs were selected and performed...
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doaj-8c07c3adbe184bf792e3b8c64be2780b2020-11-25T02:07:03ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-10-01710n/an/a10.1002/mgg3.944Influence of validating the parental origin on the clinical interpretation of fetal copy number variations in 141 core family casesPanlai Shi0Rui Li1Conghui Wang2Xiangdong Kong3Genetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaGenetic and Prenatal Screening Center Maternal and Child Health Hospital of Jiaozuo Jiozuo ChinaGenetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaGenetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaAbstract Background The sources and variants types of the copy number variations (CNVs) in prenatal fetal, and the critical role of parental origin on the interpretation of fetal CNVs are unclear. Methods One hundred and forty‐one prenatal core families with abnormal CNVs were selected and performed by low‐coverage massively parallel CNV sequencing (CNV‐seq). Results The data showed that 72.3% of fetal CNVs were derived from parents, and 27.7% were new variations. Sixty‐three cases were heterozygous deletion, 70 cases were threefold duplication, six cases were complex deletion and duplication, and two cases were fourfold repeats. That means the rate of heterozygous deletion and duplication was approximate one. In addition, in parental‐derived fetal abnormal CNVs reports, before validating parental origin, 62 CNVs were variants of uncertain significance (VUS), 15 CNVs were likely benign, 20 CNVs were likely pathogenic, and 5 CNVs were pathogenic. However, after validating parental origin, the total clinical significance changed into 12 VUS, 89 likely benign, 1 likely pathogenic, and 0 pathogenic. The clinical interpretation of 78.4% fetal CNVs was changed and tended to be benign after parental CNVs were detected. Besides, we followed up all families. 93.3% parental‐derived fetal and 30.3% fetus in new mutation group were born healthy. Conclusion Parental origin verification has an important significance for interpretation on the clinical significance of fetal CNVs.https://doi.org/10.1002/mgg3.944clinical interpretationCNV‐seqcopy number variations (CNVs)parental origin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Panlai Shi Rui Li Conghui Wang Xiangdong Kong |
spellingShingle |
Panlai Shi Rui Li Conghui Wang Xiangdong Kong Influence of validating the parental origin on the clinical interpretation of fetal copy number variations in 141 core family cases Molecular Genetics & Genomic Medicine clinical interpretation CNV‐seq copy number variations (CNVs) parental origin |
author_facet |
Panlai Shi Rui Li Conghui Wang Xiangdong Kong |
author_sort |
Panlai Shi |
title |
Influence of validating the parental origin on the clinical interpretation of fetal copy number variations in 141 core family cases |
title_short |
Influence of validating the parental origin on the clinical interpretation of fetal copy number variations in 141 core family cases |
title_full |
Influence of validating the parental origin on the clinical interpretation of fetal copy number variations in 141 core family cases |
title_fullStr |
Influence of validating the parental origin on the clinical interpretation of fetal copy number variations in 141 core family cases |
title_full_unstemmed |
Influence of validating the parental origin on the clinical interpretation of fetal copy number variations in 141 core family cases |
title_sort |
influence of validating the parental origin on the clinical interpretation of fetal copy number variations in 141 core family cases |
publisher |
Wiley |
series |
Molecular Genetics & Genomic Medicine |
issn |
2324-9269 |
publishDate |
2019-10-01 |
description |
Abstract Background The sources and variants types of the copy number variations (CNVs) in prenatal fetal, and the critical role of parental origin on the interpretation of fetal CNVs are unclear. Methods One hundred and forty‐one prenatal core families with abnormal CNVs were selected and performed by low‐coverage massively parallel CNV sequencing (CNV‐seq). Results The data showed that 72.3% of fetal CNVs were derived from parents, and 27.7% were new variations. Sixty‐three cases were heterozygous deletion, 70 cases were threefold duplication, six cases were complex deletion and duplication, and two cases were fourfold repeats. That means the rate of heterozygous deletion and duplication was approximate one. In addition, in parental‐derived fetal abnormal CNVs reports, before validating parental origin, 62 CNVs were variants of uncertain significance (VUS), 15 CNVs were likely benign, 20 CNVs were likely pathogenic, and 5 CNVs were pathogenic. However, after validating parental origin, the total clinical significance changed into 12 VUS, 89 likely benign, 1 likely pathogenic, and 0 pathogenic. The clinical interpretation of 78.4% fetal CNVs was changed and tended to be benign after parental CNVs were detected. Besides, we followed up all families. 93.3% parental‐derived fetal and 30.3% fetus in new mutation group were born healthy. Conclusion Parental origin verification has an important significance for interpretation on the clinical significance of fetal CNVs. |
topic |
clinical interpretation CNV‐seq copy number variations (CNVs) parental origin |
url |
https://doi.org/10.1002/mgg3.944 |
work_keys_str_mv |
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