دورية أكاديمية
Detecting Low-Variant Allele Frequency Mosaic Pathogenic Variants of NF1, TSC2, and AKT3 Genes from Blood in Patients with Neurodevelopmental Disorders.
| العنوان: | Detecting Low-Variant Allele Frequency Mosaic Pathogenic Variants of NF1, TSC2, and AKT3 Genes from Blood in Patients with Neurodevelopmental Disorders. |
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| المؤلفون: | Kim SH; Pediatric Neurology, Department of Pediatrics, Epilepsy Research Institute, Yonsei University College of Medicine, Severance Children's Hospital, Seoul, Republic of Korea., Kwon SS; Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea., Park MR; Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea., Lee HA; Department of Laboratory Medicine, Graduate School of Medical Science, Brain Korea 21 PLUS Project, Yonsei University College of Medicine, Seoul, Republic of Korea., Kim JH; Pediatric Neurology, Department of Pediatrics, Epilepsy Research Institute, Yonsei University College of Medicine, Severance Children's Hospital, Seoul, Republic of Korea., Cha J; Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Kim S; Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea; Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea., Baek ST; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea., Kim SH; Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea., Lee JS; Pediatric Neurology, Department of Pediatrics, Epilepsy Research Institute, Yonsei University College of Medicine, Severance Children's Hospital, Seoul, Republic of Korea., Kim HD; Pediatric Neurology, Department of Pediatrics, Epilepsy Research Institute, Yonsei University College of Medicine, Severance Children's Hospital, Seoul, Republic of Korea., Choi JR; Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Dxome, Seoul, Republic of Korea., Lee ST; Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Dxome, Seoul, Republic of Korea. Electronic address: lee.st@yuhs.ac., Kang HC; Pediatric Neurology, Department of Pediatrics, Epilepsy Research Institute, Yonsei University College of Medicine, Severance Children's Hospital, Seoul, Republic of Korea. Electronic address: hipo0207@yuhs.ac. |
| المصدر: | The Journal of molecular diagnostics : JMD [J Mol Diagn] 2023 Aug; Vol. 25 (8), pp. 583-591. Date of Electronic Publication: 2023 Apr 22. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 100893612 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1943-7811 (Electronic) Linking ISSN: 15251578 NLM ISO Abbreviation: J Mol Diagn Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2011- : New York : Elsevier Original Publication: Bethesda, MD : American Society for Investigative Pathology and the Association for Molecular Pathology, 1999- |
| مواضيع طبية MeSH: | Brain Diseases* , Neurocutaneous Syndromes* , Neurodevelopmental Disorders*, Humans ; Gene Frequency ; High-Throughput Nucleotide Sequencing/methods ; Mosaicism ; Mutation ; Proto-Oncogene Proteins c-akt/genetics |
| مستخلص: | Growing evidence indicates that early and late postzygotic mosaicism can cause neurodevelopmental disorders (NDDs), but detection of low variant allele frequency (VAF) mosaic variants from blood remains a challenge. Data of 2162 patients with NDDs who underwent conventional genetic tests were reviewed and a deep sequencing was performed using a specifically designed mosaic next-generation sequencing (NGS) panel in the patients with negative genetic test results. Forty-four patents with neurocutaneous syndrome, malformation of cortical development, or nonlesional epileptic encephalopathies were included. In total, mosaic variants were detected from blood in 1.2% (25/2162) of the patients. Using conventional NGS panels, 22 mosaic variants (VAF, 8.8% to 29.8%) were identified in 18 different genes. Using a specifically designed mosaicism NGS panel, three mosaic variants of the NF1, TSC2, and AKT3 genes were identified (VAF, 2.0% to 11.2%). Mosaic variants were found frequently in the patients who had neurocutaneous syndrome (2/7, 28.6%), whereas only one or no mosaic variant was detected for patients who had malformations of cortical development (1/20, 5%) or nonlesional epileptic encephalopathies (0%, 0/17). In summary, mosaic variants that contribute to the spectrum of NDDs can be detected from blood via conventional NGS and specifically designed mosaicism NGS panels, and detection of mosaic variants using blood will increase diagnostic yield. (Copyright © 2023 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.) |
| المشرفين على المادة: | EC 2.7.11.1 (AKT3 protein, human) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) 0 (TSC2 protein, human) 0 (NF1 protein, human) |
| تواريخ الأحداث: | Date Created: 20230423 Date Completed: 20230803 Latest Revision: 20230803 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.jmoldx.2023.04.003 |
| PMID: | 37088138 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1943-7811 |
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| DOI: | 10.1016/j.jmoldx.2023.04.003 |