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Noninvasive Prenatal Testing of Methylmalonic Acidemia cblC Type Using the cSMART Assay for MMACHC Gene Mutations

Noninvasive prenatal testing (NIPT) for monogenic disorders has been developed in recent years; however, there are still significant technical and analytical challenges for clinical use. The clinical feasibility of NIPT for methylmalonic acidemia cblC type (cblC type MMA) was investigated using our...

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Autores principales: Lv, Weigang, Liang, Lili, Chen, Xin, Li, Zhuo, Liang, Desheng, Zhu, Huimin, Teng, Yanling, Wu, Weijuan, Wu, Lingqian, Han, Lianshu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777107/
https://www.ncbi.nlm.nih.gov/pubmed/35069678
http://dx.doi.org/10.3389/fgene.2021.750719
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author Lv, Weigang
Liang, Lili
Chen, Xin
Li, Zhuo
Liang, Desheng
Zhu, Huimin
Teng, Yanling
Wu, Weijuan
Wu, Lingqian
Han, Lianshu
author_facet Lv, Weigang
Liang, Lili
Chen, Xin
Li, Zhuo
Liang, Desheng
Zhu, Huimin
Teng, Yanling
Wu, Weijuan
Wu, Lingqian
Han, Lianshu
author_sort Lv, Weigang
collection PubMed
description Noninvasive prenatal testing (NIPT) for monogenic disorders has been developed in recent years; however, there are still significant technical and analytical challenges for clinical use. The clinical feasibility of NIPT for methylmalonic acidemia cblC type (cblC type MMA) was investigated using our circulating single-molecule amplification and re-sequencing technology (cSMART). Trios molecular diagnosis was performed in 29 cblC type MMA-affected children and their parents by traditional Sanger sequencing. In the second pregnancy, invasive prenatal diagnosis (IPD) of the pathogenic MMACHC gene was used to determine fetal genotypes, and NIPT was performed using a novel MMACHC gene–specific cSMART assay. Maternal–fetal genotypes were deduced based on the mutation ratio in maternal plasma DNA. Concordance of fetal genotypes between IPD and NIPT, and the sensitivity and specificity of NIPT were determined. After removing two cases with a low P value or reads, the concordance ratio for NIPT and IPD was 100.00% (27/27), and the sensitivity and specificity were 100.00% (54.07–100.00%) and 100.00% (83.89–100.00%), respectively. This study demonstrates that NIPT using the cSMART assay for cblC type MMA was accurate in detecting fetal genotypes. cSMART has a potential clinical application as a prenatal diagnosis and screening tool for carrier and low-risk genotypes of cblC type MMA and other monogenic diseases.
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spelling pubmed-87771072022-01-22 Noninvasive Prenatal Testing of Methylmalonic Acidemia cblC Type Using the cSMART Assay for MMACHC Gene Mutations Lv, Weigang Liang, Lili Chen, Xin Li, Zhuo Liang, Desheng Zhu, Huimin Teng, Yanling Wu, Weijuan Wu, Lingqian Han, Lianshu Front Genet Genetics Noninvasive prenatal testing (NIPT) for monogenic disorders has been developed in recent years; however, there are still significant technical and analytical challenges for clinical use. The clinical feasibility of NIPT for methylmalonic acidemia cblC type (cblC type MMA) was investigated using our circulating single-molecule amplification and re-sequencing technology (cSMART). Trios molecular diagnosis was performed in 29 cblC type MMA-affected children and their parents by traditional Sanger sequencing. In the second pregnancy, invasive prenatal diagnosis (IPD) of the pathogenic MMACHC gene was used to determine fetal genotypes, and NIPT was performed using a novel MMACHC gene–specific cSMART assay. Maternal–fetal genotypes were deduced based on the mutation ratio in maternal plasma DNA. Concordance of fetal genotypes between IPD and NIPT, and the sensitivity and specificity of NIPT were determined. After removing two cases with a low P value or reads, the concordance ratio for NIPT and IPD was 100.00% (27/27), and the sensitivity and specificity were 100.00% (54.07–100.00%) and 100.00% (83.89–100.00%), respectively. This study demonstrates that NIPT using the cSMART assay for cblC type MMA was accurate in detecting fetal genotypes. cSMART has a potential clinical application as a prenatal diagnosis and screening tool for carrier and low-risk genotypes of cblC type MMA and other monogenic diseases. Frontiers Media S.A. 2022-01-07 /pmc/articles/PMC8777107/ /pubmed/35069678 http://dx.doi.org/10.3389/fgene.2021.750719 Text en Copyright © 2022 Lv, Liang, Chen, Li, Liang, Zhu, Teng, Wu, Wu and Han. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Lv, Weigang
Liang, Lili
Chen, Xin
Li, Zhuo
Liang, Desheng
Zhu, Huimin
Teng, Yanling
Wu, Weijuan
Wu, Lingqian
Han, Lianshu
Noninvasive Prenatal Testing of Methylmalonic Acidemia cblC Type Using the cSMART Assay for MMACHC Gene Mutations
title Noninvasive Prenatal Testing of Methylmalonic Acidemia cblC Type Using the cSMART Assay for MMACHC Gene Mutations
title_full Noninvasive Prenatal Testing of Methylmalonic Acidemia cblC Type Using the cSMART Assay for MMACHC Gene Mutations
title_fullStr Noninvasive Prenatal Testing of Methylmalonic Acidemia cblC Type Using the cSMART Assay for MMACHC Gene Mutations
title_full_unstemmed Noninvasive Prenatal Testing of Methylmalonic Acidemia cblC Type Using the cSMART Assay for MMACHC Gene Mutations
title_short Noninvasive Prenatal Testing of Methylmalonic Acidemia cblC Type Using the cSMART Assay for MMACHC Gene Mutations
title_sort noninvasive prenatal testing of methylmalonic acidemia cblc type using the csmart assay for mmachc gene mutations
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777107/
https://www.ncbi.nlm.nih.gov/pubmed/35069678
http://dx.doi.org/10.3389/fgene.2021.750719
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