Renata Szalai , Agnes Till , Attila Gyenesei , Judit Bene , Kinga Hadzsiev
{"title":"WES在胎儿基因诊断中的重要性和应用:在小头畸形胎儿中发现新型 ASPM 基因突变","authors":"Renata Szalai , Agnes Till , Attila Gyenesei , Judit Bene , Kinga Hadzsiev","doi":"10.1016/j.ymgmr.2024.101056","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Prenatal whole exome sequencing (WES) approaches can provide genetic diagnosis with rapid turnaround time and high diagnostic rate when conventional tests are negative. Here we report a family with multiple pregnancy loss and with repeated occurrence of fetal microcephaly.</p></div><div><h3>Methods and results</h3><p>Because of positive family history and recurrent structural abnormality during the pregnancies that may lead postnatal neurodevelopmental consequences, WES analysis was indicated. Umbilical cord blood sampling was carried out and WES was performed using Twist Human Core Exome Kit and Illumina sequencing technology. The presence of pathogenic variants was confirmed by Sanger sequencing. WES analysis revealed a known pathogenic c.8506_8507delCA (p.Gln2836Glufs*35, rs587783280) and a novel pathogenic c.3134_3135delTC (p.Leu1045Glnfs*17) <em>ASPM</em> mutations in the fetus in compound heterozygous state. The c.3134_3135delTC has never been reported in the literature.</p></div><div><h3>Conclusions</h3><p>Our findings serve additional evidence that WES can be an efficient and relevant tool to diagnose certain genetic disorders with appropriate indication and to assess the recurrence risk of a disease. With the application of WES in combination with pre-implantation genetic tests, we can avoid the transmission of pathogenic mutations and we can achieve a decreased abortion rate in obstetric care.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000090/pdfft?md5=a734c9c72cbe5e93f65df382fd7305b0&pid=1-s2.0-S2214426924000090-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Importance and application of WES in fetal genetic diagnostics: Identification of novel ASPM mutation in a fetus with microcephaly\",\"authors\":\"Renata Szalai , Agnes Till , Attila Gyenesei , Judit Bene , Kinga Hadzsiev\",\"doi\":\"10.1016/j.ymgmr.2024.101056\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Prenatal whole exome sequencing (WES) approaches can provide genetic diagnosis with rapid turnaround time and high diagnostic rate when conventional tests are negative. Here we report a family with multiple pregnancy loss and with repeated occurrence of fetal microcephaly.</p></div><div><h3>Methods and results</h3><p>Because of positive family history and recurrent structural abnormality during the pregnancies that may lead postnatal neurodevelopmental consequences, WES analysis was indicated. Umbilical cord blood sampling was carried out and WES was performed using Twist Human Core Exome Kit and Illumina sequencing technology. The presence of pathogenic variants was confirmed by Sanger sequencing. WES analysis revealed a known pathogenic c.8506_8507delCA (p.Gln2836Glufs*35, rs587783280) and a novel pathogenic c.3134_3135delTC (p.Leu1045Glnfs*17) <em>ASPM</em> mutations in the fetus in compound heterozygous state. The c.3134_3135delTC has never been reported in the literature.</p></div><div><h3>Conclusions</h3><p>Our findings serve additional evidence that WES can be an efficient and relevant tool to diagnose certain genetic disorders with appropriate indication and to assess the recurrence risk of a disease. With the application of WES in combination with pre-implantation genetic tests, we can avoid the transmission of pathogenic mutations and we can achieve a decreased abortion rate in obstetric care.</p></div>\",\"PeriodicalId\":18814,\"journal\":{\"name\":\"Molecular Genetics and Metabolism Reports\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2024-01-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2214426924000090/pdfft?md5=a734c9c72cbe5e93f65df382fd7305b0&pid=1-s2.0-S2214426924000090-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Genetics and Metabolism Reports\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2214426924000090\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Genetics and Metabolism Reports","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2214426924000090","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Importance and application of WES in fetal genetic diagnostics: Identification of novel ASPM mutation in a fetus with microcephaly
Background
Prenatal whole exome sequencing (WES) approaches can provide genetic diagnosis with rapid turnaround time and high diagnostic rate when conventional tests are negative. Here we report a family with multiple pregnancy loss and with repeated occurrence of fetal microcephaly.
Methods and results
Because of positive family history and recurrent structural abnormality during the pregnancies that may lead postnatal neurodevelopmental consequences, WES analysis was indicated. Umbilical cord blood sampling was carried out and WES was performed using Twist Human Core Exome Kit and Illumina sequencing technology. The presence of pathogenic variants was confirmed by Sanger sequencing. WES analysis revealed a known pathogenic c.8506_8507delCA (p.Gln2836Glufs*35, rs587783280) and a novel pathogenic c.3134_3135delTC (p.Leu1045Glnfs*17) ASPM mutations in the fetus in compound heterozygous state. The c.3134_3135delTC has never been reported in the literature.
Conclusions
Our findings serve additional evidence that WES can be an efficient and relevant tool to diagnose certain genetic disorders with appropriate indication and to assess the recurrence risk of a disease. With the application of WES in combination with pre-implantation genetic tests, we can avoid the transmission of pathogenic mutations and we can achieve a decreased abortion rate in obstetric care.
期刊介绍:
Molecular Genetics and Metabolism Reports is an open access journal that publishes molecular and metabolic reports describing investigations that use the tools of biochemistry and molecular biology for studies of normal and diseased states. In addition to original research articles, sequence reports, brief communication reports and letters to the editor are considered.