Cargando…
Haplotype-Based Noninvasive Prenatal Diagnosis of 21 Families With Duchenne Muscular Dystrophy: Real-World Clinical Data in China
Noninvasive prenatal diagnosis (NIPD) of single-gene disorders has recently become the focus of clinical laboratories. However, reports on the clinical application of NIPD of Duchenne muscular dystrophy (DMD) are limited. This study aimed to evaluate the detection performance of haplotype-based NIPD...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712857/ https://www.ncbi.nlm.nih.gov/pubmed/34970304 http://dx.doi.org/10.3389/fgene.2021.791856 |
_version_ | 1784623649297268736 |
---|---|
author | Kong, Lingrong Li, Shaojun Zhao, Zhenhua Feng, Jun Chen, Guangquan Liu, Lina Tang, Weiqin Li, Suqing Li, Feifei Han, Xiujuan Wu, Di Zhang, Haichuan Sun, Luming Kong, Xiangdong |
author_facet | Kong, Lingrong Li, Shaojun Zhao, Zhenhua Feng, Jun Chen, Guangquan Liu, Lina Tang, Weiqin Li, Suqing Li, Feifei Han, Xiujuan Wu, Di Zhang, Haichuan Sun, Luming Kong, Xiangdong |
author_sort | Kong, Lingrong |
collection | PubMed |
description | Noninvasive prenatal diagnosis (NIPD) of single-gene disorders has recently become the focus of clinical laboratories. However, reports on the clinical application of NIPD of Duchenne muscular dystrophy (DMD) are limited. This study aimed to evaluate the detection performance of haplotype-based NIPD of DMD in a real clinical environment. Twenty-one DMD families at 7–12 weeks of gestation were prospectively recruited. DNA libraries of cell-free DNA from the pregnant and genomic DNA from family members were captured using a custom assay for the enrichment of DMD gene exons and spanning single-nucleotide polymorphisms, followed by next-generation sequencing. Parental haplotype phasing was based on family linkage analysis, and fetal genotyping was inferred using the Bayes factor through target maternal plasma sequencing. Finally, the entire experimental process was promoted in the local clinical laboratory. We recruited 13 complete families, 6 families without paternal samples, and 2 families without probands in which daughter samples were collected. Two different maternal haplotypes were constructed based on family members in all 21 pedigrees at as early as 7 gestational weeks. Among the included families, the fetal genotypes of 20 families were identified at the first blood collection, and a second blood collection was performed for another family due to low fetal concentration. The NIPD result of each family was reported within 1 week. The fetal fraction in maternal cfDNA ranged from 1.87 to 11.68%. In addition, recombination events were assessed in two fetuses. All NIPD results were concordant with the findings of invasive prenatal diagnosis (chorionic villus sampling or amniocentesis). Exon capture and haplotype-based NIPD of DMD are regularly used for DMD genetic diagnosis, carrier screening, and noninvasive prenatal diagnosis in the clinic. Our method, haplotype-based early screening for DMD fetal genotyping via cfDNA sequencing, has high feasibility and accuracy, a short turnaround time, and is inexpensive in a real clinical environment. |
format | Online Article Text |
id | pubmed-8712857 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87128572021-12-29 Haplotype-Based Noninvasive Prenatal Diagnosis of 21 Families With Duchenne Muscular Dystrophy: Real-World Clinical Data in China Kong, Lingrong Li, Shaojun Zhao, Zhenhua Feng, Jun Chen, Guangquan Liu, Lina Tang, Weiqin Li, Suqing Li, Feifei Han, Xiujuan Wu, Di Zhang, Haichuan Sun, Luming Kong, Xiangdong Front Genet Genetics Noninvasive prenatal diagnosis (NIPD) of single-gene disorders has recently become the focus of clinical laboratories. However, reports on the clinical application of NIPD of Duchenne muscular dystrophy (DMD) are limited. This study aimed to evaluate the detection performance of haplotype-based NIPD of DMD in a real clinical environment. Twenty-one DMD families at 7–12 weeks of gestation were prospectively recruited. DNA libraries of cell-free DNA from the pregnant and genomic DNA from family members were captured using a custom assay for the enrichment of DMD gene exons and spanning single-nucleotide polymorphisms, followed by next-generation sequencing. Parental haplotype phasing was based on family linkage analysis, and fetal genotyping was inferred using the Bayes factor through target maternal plasma sequencing. Finally, the entire experimental process was promoted in the local clinical laboratory. We recruited 13 complete families, 6 families without paternal samples, and 2 families without probands in which daughter samples were collected. Two different maternal haplotypes were constructed based on family members in all 21 pedigrees at as early as 7 gestational weeks. Among the included families, the fetal genotypes of 20 families were identified at the first blood collection, and a second blood collection was performed for another family due to low fetal concentration. The NIPD result of each family was reported within 1 week. The fetal fraction in maternal cfDNA ranged from 1.87 to 11.68%. In addition, recombination events were assessed in two fetuses. All NIPD results were concordant with the findings of invasive prenatal diagnosis (chorionic villus sampling or amniocentesis). Exon capture and haplotype-based NIPD of DMD are regularly used for DMD genetic diagnosis, carrier screening, and noninvasive prenatal diagnosis in the clinic. Our method, haplotype-based early screening for DMD fetal genotyping via cfDNA sequencing, has high feasibility and accuracy, a short turnaround time, and is inexpensive in a real clinical environment. Frontiers Media S.A. 2021-12-14 /pmc/articles/PMC8712857/ /pubmed/34970304 http://dx.doi.org/10.3389/fgene.2021.791856 Text en Copyright © 2021 Kong, Li, Zhao, Feng, Chen, Liu, Tang, Li, Li, Han, Wu, Zhang, Sun and Kong. 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 Kong, Lingrong Li, Shaojun Zhao, Zhenhua Feng, Jun Chen, Guangquan Liu, Lina Tang, Weiqin Li, Suqing Li, Feifei Han, Xiujuan Wu, Di Zhang, Haichuan Sun, Luming Kong, Xiangdong Haplotype-Based Noninvasive Prenatal Diagnosis of 21 Families With Duchenne Muscular Dystrophy: Real-World Clinical Data in China |
title | Haplotype-Based Noninvasive Prenatal Diagnosis of 21 Families With Duchenne Muscular Dystrophy: Real-World Clinical Data in China |
title_full | Haplotype-Based Noninvasive Prenatal Diagnosis of 21 Families With Duchenne Muscular Dystrophy: Real-World Clinical Data in China |
title_fullStr | Haplotype-Based Noninvasive Prenatal Diagnosis of 21 Families With Duchenne Muscular Dystrophy: Real-World Clinical Data in China |
title_full_unstemmed | Haplotype-Based Noninvasive Prenatal Diagnosis of 21 Families With Duchenne Muscular Dystrophy: Real-World Clinical Data in China |
title_short | Haplotype-Based Noninvasive Prenatal Diagnosis of 21 Families With Duchenne Muscular Dystrophy: Real-World Clinical Data in China |
title_sort | haplotype-based noninvasive prenatal diagnosis of 21 families with duchenne muscular dystrophy: real-world clinical data in china |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712857/ https://www.ncbi.nlm.nih.gov/pubmed/34970304 http://dx.doi.org/10.3389/fgene.2021.791856 |
work_keys_str_mv | AT konglingrong haplotypebasednoninvasiveprenataldiagnosisof21familieswithduchennemusculardystrophyrealworldclinicaldatainchina AT lishaojun haplotypebasednoninvasiveprenataldiagnosisof21familieswithduchennemusculardystrophyrealworldclinicaldatainchina AT zhaozhenhua haplotypebasednoninvasiveprenataldiagnosisof21familieswithduchennemusculardystrophyrealworldclinicaldatainchina AT fengjun haplotypebasednoninvasiveprenataldiagnosisof21familieswithduchennemusculardystrophyrealworldclinicaldatainchina AT chenguangquan haplotypebasednoninvasiveprenataldiagnosisof21familieswithduchennemusculardystrophyrealworldclinicaldatainchina AT liulina haplotypebasednoninvasiveprenataldiagnosisof21familieswithduchennemusculardystrophyrealworldclinicaldatainchina AT tangweiqin haplotypebasednoninvasiveprenataldiagnosisof21familieswithduchennemusculardystrophyrealworldclinicaldatainchina AT lisuqing haplotypebasednoninvasiveprenataldiagnosisof21familieswithduchennemusculardystrophyrealworldclinicaldatainchina AT lifeifei haplotypebasednoninvasiveprenataldiagnosisof21familieswithduchennemusculardystrophyrealworldclinicaldatainchina AT hanxiujuan haplotypebasednoninvasiveprenataldiagnosisof21familieswithduchennemusculardystrophyrealworldclinicaldatainchina AT wudi haplotypebasednoninvasiveprenataldiagnosisof21familieswithduchennemusculardystrophyrealworldclinicaldatainchina AT zhanghaichuan haplotypebasednoninvasiveprenataldiagnosisof21familieswithduchennemusculardystrophyrealworldclinicaldatainchina AT sunluming haplotypebasednoninvasiveprenataldiagnosisof21familieswithduchennemusculardystrophyrealworldclinicaldatainchina AT kongxiangdong haplotypebasednoninvasiveprenataldiagnosisof21familieswithduchennemusculardystrophyrealworldclinicaldatainchina |