Genetic Testing for Malformations of Cortical Development: A Clinical Diagnostic Study. Straka, B., Hermanovska, B., Krskova, L., Zamecnik, J., Vlckova, M., Balascakova, M., Tesner, P., Jezdik, P., Tichy, M., Kyncl, M., Musilova, A., Lassuthova, P., Marusic, P., Krsek, P., & Group, o. b. o. t. M. P. S. Neurology Genetics, September, 2022. Publisher: Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology Section: Research Article
Genetic Testing for Malformations of Cortical Development: A Clinical Diagnostic Study [link]Paper  doi  abstract   bibtex   
Background and Objectives Malformations of cortical development (MCD), though individually rare, constitute a significant burden of disease. The diagnostic yield of next-generation sequencing (NGS) in these patients varies across studies and methods, and novel genes and variants continue to emerge. Methods Patients (n = 123) with a definite radiologic or histopathologic diagnosis of MCD, with or without epilepsy were included in this study. They underwent NGS-based targeted gene panel (TGP) testing, whole-exome sequencing (WES), or WES-based virtual panel testing. Selected patients who underwent epilepsy surgery (n = 69) also had somatic gene testing of brain tissue–derived DNA. We analyzed predictors of positive germline genetic finding and diagnostic yield of respective methods. Results Pathogenic or likely pathogenic germline genetic variants were detected in 21% of patients (26/123). In the surgical subgroup (69/123), we performed somatic sequencing in 40% of cases (28/69) and detected causal variants in 18% (5/28). Diagnostic yield did not differ between TGP, WES-based virtual gene panel, and open WES (p = 0.69). Diagnosis of focal cortical dysplasia type 2A, epilepsy, and intellectual disability were associated with positive results of germline testing. We report previously unpublished variants in 16/26 patients and 4 cases of MCD with likely pathogenic variants in non-MCD genes. Discussion In this study, we are reporting genetic findings of a large cohort of MCD patients with epilepsy or potentially epileptogenic MCD. We determine predictors of successful ascertainment of a genetic diagnosis in real-life setting and report novel, likely pathogenic variants in MCD and non-MCD genes alike.
@article{straka_genetic_2022,
	title = {Genetic {Testing} for {Malformations} of {Cortical} {Development}: {A} {Clinical} {Diagnostic} {Study}},
	volume = {8},
	copyright = {Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.},
	issn = {2376-7839},
	shorttitle = {Genetic {Testing} for {Malformations} of {Cortical} {Development}},
	url = {https://ng.neurology.org/content/8/5/e200032},
	doi = {10.1212/NXG.0000000000200032},
	abstract = {Background and Objectives Malformations of cortical development (MCD), though individually rare, constitute a significant burden of disease. The diagnostic yield of next-generation sequencing (NGS) in these patients varies across studies and methods, and novel genes and variants continue to emerge.
Methods Patients (n = 123) with a definite radiologic or histopathologic diagnosis of MCD, with or without epilepsy were included in this study. They underwent NGS-based targeted gene panel (TGP) testing, whole-exome sequencing (WES), or WES-based virtual panel testing. Selected patients who underwent epilepsy surgery (n = 69) also had somatic gene testing of brain tissue–derived DNA. We analyzed predictors of positive germline genetic finding and diagnostic yield of respective methods.
Results Pathogenic or likely pathogenic germline genetic variants were detected in 21\% of patients (26/123). In the surgical subgroup (69/123), we performed somatic sequencing in 40\% of cases (28/69) and detected causal variants in 18\% (5/28). Diagnostic yield did not differ between TGP, WES-based virtual gene panel, and open WES (p = 0.69). Diagnosis of focal cortical dysplasia type 2A, epilepsy, and intellectual disability were associated with positive results of germline testing. We report previously unpublished variants in 16/26 patients and 4 cases of MCD with likely pathogenic variants in non-MCD genes.
Discussion In this study, we are reporting genetic findings of a large cohort of MCD patients with epilepsy or potentially epileptogenic MCD. We determine predictors of successful ascertainment of a genetic diagnosis in real-life setting and report novel, likely pathogenic variants in MCD and non-MCD genes alike.},
	language = {en},
	number = {5},
	urldate = {2022-12-13},
	journal = {Neurology Genetics},
	author = {Straka, Barbora and Hermanovska, Barbora and Krskova, Lenka and Zamecnik, Josef and Vlckova, Marketa and Balascakova, Miroslava and Tesner, Pavel and Jezdik, Petr and Tichy, Michal and Kyncl, Martin and Musilova, Alena and Lassuthova, Petra and Marusic, Petr and Krsek, Pavel and Group, on behalf of the MCD Prague Study},
	month = sep,
	year = {2022},
	note = {Publisher: Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Section: Research Article},
	keywords = {Alamut},
}
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