Karolina Ewa Matuszewska, Ewelina Bukowska-Olech, Michał Piechota, Katarzyna Staniek-Łacna, Krzysztof Drews, Barbara Więckowska, Grzegorz Koczyk, Delfina Popiel, Adam Dawidziuk, Natalia Kochalska, Katarzyna Milanowska, Agnieszka Białek-Prościńska, Jana Skrzypczak, Adam Sebastian Hirschfeld, Aleksandra Wnuk-Kłosińska, Marzena Wiśniewska, Aleksander Jamsheer, Anna Latos-Bieleńska
{"title":"从染色体畸变到单个基因突变--流产后绒毛膜基因研究对寻找流产原因的意义。","authors":"Karolina Ewa Matuszewska, Ewelina Bukowska-Olech, Michał Piechota, Katarzyna Staniek-Łacna, Krzysztof Drews, Barbara Więckowska, Grzegorz Koczyk, Delfina Popiel, Adam Dawidziuk, Natalia Kochalska, Katarzyna Milanowska, Agnieszka Białek-Prościńska, Jana Skrzypczak, Adam Sebastian Hirschfeld, Aleksandra Wnuk-Kłosińska, Marzena Wiśniewska, Aleksander Jamsheer, Anna Latos-Bieleńska","doi":"10.1080/14767058.2024.2364249","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To determine the frequency of chromosomal aberrations in chorions after a miscarriage. The second was to examine selected euploid chorions using a next-generation sequencing (NGS) panel designed to assess 43 genes associated with pregnancy loss.</p><p><strong>Materials and methods: </strong>The 1244 chorions were tested by targeted quantitative fluorescent PCR (QF-PCR, 827 chorions) and microarray-based comparative genomic hybridization (aCGH, 417 chorions). Then, 9 euploid chorions were examined using a designed NGS panel.</p><p><strong>Results: </strong>Trisomies were the most common chromosomal aberration identified in the spontaneous miscarriage samples. The second chromosomal abnormality in the aCGH group and the third most common in the QF-PCR group was monosomy X. Structural aberrations were the third most common aberration in the samples screened by aCGH (7.7% of chorions). In 19% of 647 couples who submitted chorions for analysis after pregnancy loss, the chromosomal abnormality in the chorion originated from a woman with a balanced chromosomal rearrangement. This discovery was statistically significant compared to patients with normal chorions. Using the designed NGS panel, we identified a potentially pathogenic de novo variant in the <i>F5</i> gene in two euploid chorions. Additionally, among the patients who experienced miscarriages and were screened using the NGS panel, we identified variants in the <i>MDM</i>, <i>ACE</i>, and <i>NLRP2</i> genes that could be associated with a predisposition to pregnancy loss.</p><p><strong>Conclusion: </strong>Numerical aberrations are the most common cause of miscarriages, but structural chromosomal aberrations also account for a significant proportion of abnormal results. Our findings indicate that couples with structural chromosomal abnormalities in material post-miscarriage are at increased risk of carrying balanced chromosomal abnormalities. Moreover, NGS-based analyses can uncover previously unidentified causes of miscarriages in the chorionic villi.</p>","PeriodicalId":50146,"journal":{"name":"Journal of Maternal-Fetal & Neonatal Medicine","volume":"37 1","pages":"2364249"},"PeriodicalIF":1.7000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"From chromosomal aberrations to mutations in individual genes - the significance of genetic studies of chorions after miscarriage in the search for causes of miscarriages.\",\"authors\":\"Karolina Ewa Matuszewska, Ewelina Bukowska-Olech, Michał Piechota, Katarzyna Staniek-Łacna, Krzysztof Drews, Barbara Więckowska, Grzegorz Koczyk, Delfina Popiel, Adam Dawidziuk, Natalia Kochalska, Katarzyna Milanowska, Agnieszka Białek-Prościńska, Jana Skrzypczak, Adam Sebastian Hirschfeld, Aleksandra Wnuk-Kłosińska, Marzena Wiśniewska, Aleksander Jamsheer, Anna Latos-Bieleńska\",\"doi\":\"10.1080/14767058.2024.2364249\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To determine the frequency of chromosomal aberrations in chorions after a miscarriage. The second was to examine selected euploid chorions using a next-generation sequencing (NGS) panel designed to assess 43 genes associated with pregnancy loss.</p><p><strong>Materials and methods: </strong>The 1244 chorions were tested by targeted quantitative fluorescent PCR (QF-PCR, 827 chorions) and microarray-based comparative genomic hybridization (aCGH, 417 chorions). Then, 9 euploid chorions were examined using a designed NGS panel.</p><p><strong>Results: </strong>Trisomies were the most common chromosomal aberration identified in the spontaneous miscarriage samples. The second chromosomal abnormality in the aCGH group and the third most common in the QF-PCR group was monosomy X. Structural aberrations were the third most common aberration in the samples screened by aCGH (7.7% of chorions). In 19% of 647 couples who submitted chorions for analysis after pregnancy loss, the chromosomal abnormality in the chorion originated from a woman with a balanced chromosomal rearrangement. This discovery was statistically significant compared to patients with normal chorions. Using the designed NGS panel, we identified a potentially pathogenic de novo variant in the <i>F5</i> gene in two euploid chorions. Additionally, among the patients who experienced miscarriages and were screened using the NGS panel, we identified variants in the <i>MDM</i>, <i>ACE</i>, and <i>NLRP2</i> genes that could be associated with a predisposition to pregnancy loss.</p><p><strong>Conclusion: </strong>Numerical aberrations are the most common cause of miscarriages, but structural chromosomal aberrations also account for a significant proportion of abnormal results. Our findings indicate that couples with structural chromosomal abnormalities in material post-miscarriage are at increased risk of carrying balanced chromosomal abnormalities. 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From chromosomal aberrations to mutations in individual genes - the significance of genetic studies of chorions after miscarriage in the search for causes of miscarriages.
Objective: To determine the frequency of chromosomal aberrations in chorions after a miscarriage. The second was to examine selected euploid chorions using a next-generation sequencing (NGS) panel designed to assess 43 genes associated with pregnancy loss.
Materials and methods: The 1244 chorions were tested by targeted quantitative fluorescent PCR (QF-PCR, 827 chorions) and microarray-based comparative genomic hybridization (aCGH, 417 chorions). Then, 9 euploid chorions were examined using a designed NGS panel.
Results: Trisomies were the most common chromosomal aberration identified in the spontaneous miscarriage samples. The second chromosomal abnormality in the aCGH group and the third most common in the QF-PCR group was monosomy X. Structural aberrations were the third most common aberration in the samples screened by aCGH (7.7% of chorions). In 19% of 647 couples who submitted chorions for analysis after pregnancy loss, the chromosomal abnormality in the chorion originated from a woman with a balanced chromosomal rearrangement. This discovery was statistically significant compared to patients with normal chorions. Using the designed NGS panel, we identified a potentially pathogenic de novo variant in the F5 gene in two euploid chorions. Additionally, among the patients who experienced miscarriages and were screened using the NGS panel, we identified variants in the MDM, ACE, and NLRP2 genes that could be associated with a predisposition to pregnancy loss.
Conclusion: Numerical aberrations are the most common cause of miscarriages, but structural chromosomal aberrations also account for a significant proportion of abnormal results. Our findings indicate that couples with structural chromosomal abnormalities in material post-miscarriage are at increased risk of carrying balanced chromosomal abnormalities. Moreover, NGS-based analyses can uncover previously unidentified causes of miscarriages in the chorionic villi.
期刊介绍:
The official journal of The European Association of Perinatal Medicine, The Federation of Asia and Oceania Perinatal Societies and The International Society of Perinatal Obstetricians. The journal publishes a wide range of peer-reviewed research on the obstetric, medical, genetic, mental health and surgical complications of pregnancy and their effects on the mother, fetus and neonate. Research on audit, evaluation and clinical care in maternal-fetal and perinatal medicine is also featured.