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Influence of validating the parental origin on the clinical interpretation of fetal copy number variations in 141 core family cases

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...

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Autores principales: Shi, Panlai, Li, Rui, Wang, Conghui, Kong, Xiangdong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785431/
https://www.ncbi.nlm.nih.gov/pubmed/31475483
http://dx.doi.org/10.1002/mgg3.944
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author Shi, Panlai
Li, Rui
Wang, Conghui
Kong, Xiangdong
author_facet Shi, Panlai
Li, Rui
Wang, Conghui
Kong, Xiangdong
author_sort Shi, Panlai
collection PubMed
description 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.
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spelling pubmed-67854312019-10-17 Influence of validating the parental origin on the clinical interpretation of fetal copy number variations in 141 core family cases Shi, Panlai Li, Rui Wang, Conghui Kong, Xiangdong Mol Genet Genomic Med Original Articles 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. John Wiley and Sons Inc. 2019-09-01 /pmc/articles/PMC6785431/ /pubmed/31475483 http://dx.doi.org/10.1002/mgg3.944 Text en © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Shi, Panlai
Li, Rui
Wang, Conghui
Kong, Xiangdong
Influence of validating the parental origin on the clinical interpretation of fetal copy number variations in 141 core family cases
title 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_short 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
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785431/
https://www.ncbi.nlm.nih.gov/pubmed/31475483
http://dx.doi.org/10.1002/mgg3.944
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