Genetic variant interpretation for the neurologist - A pragmatic approach in the next-generation sequencing era in childhood epilepsy.

Autor: Fasaludeen A; Dept of Neurology, Sree Chitra Tirunal Institute for Medical Sciences & Technology (SCTIMST), Thiruvananthapuram, Kerala, India., McTague A; Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Department of Neurology, Great Ormond Street Hospital, London, United Kingdom., Jose M; Dept of Neurology, Sree Chitra Tirunal Institute for Medical Sciences & Technology (SCTIMST), Thiruvananthapuram, Kerala, India., Banerjee M; Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India., Sundaram S; Dept of Neurology, Sree Chitra Tirunal Institute for Medical Sciences & Technology (SCTIMST), Thiruvananthapuram, Kerala, India., Madhusoodanan UK; Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences & Technology (SCTIMST), Thiruvananthapuram, Kerala, India., Radhakrishnan A; Dept of Neurology, Sree Chitra Tirunal Institute for Medical Sciences & Technology (SCTIMST), Thiruvananthapuram, Kerala, India., Menon RN; Dept of Neurology, Sree Chitra Tirunal Institute for Medical Sciences & Technology (SCTIMST), Thiruvananthapuram, Kerala, India. Electronic address: rsnmenon@yahoo.com.
Jazyk: angličtina
Zdroj: Epilepsy research [Epilepsy Res] 2024 Mar; Vol. 201, pp. 107341. Date of Electronic Publication: 2024 Mar 02.
DOI: 10.1016/j.eplepsyres.2024.107341
Abstrakt: Genetic advances over the past decade have enhanced our understanding of the genetic landscape of childhood epilepsy. However a major challenge for clinicians ha been understanding the rationale and systematic approach towards interpretation of the clinical significance of variant(s) detected in their patients. As the clinical paradigm evolves from gene panels to whole exome or whole genome testing including rapid genome sequencing, the number of patients tested and variants identified per patient will only increase. Each step in the process of variant interpretation has limitations and there is no single criterion which enables the clinician to draw reliable conclusions on a causal relationship between the variant and disease without robust clinical phenotyping. Although many automated online analysis software tools are available, these carry a risk of misinterpretation. This guideline provides a pragmatic, real-world approach to variant interpretation for the child neurologist. The focus will be on ascertaining aspects such as variant frequency, subtype, inheritance pattern, structural and functional consequence with regard to genotype-phenotype correlations, while refraining from mere interpretation of the classification provided in a genetic test report. It will not replace the expert advice of colleagues in clinical genetics, however as genomic investigations become a first-line test for epilepsy, it is vital that neurologists and epileptologists are equipped to navigate this landscape.
Competing Interests: Conflicts of interest None
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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