McTague, Amy;
Brunklaus, Andreas;
Barcia, Giulia;
Varadkar, Sophia;
Zuberi, Sameer M;
Chatron, Nicolas;
Parrini, Elena;
... Lesca, Gaetan; + view all
(2022)
Defining causal variants in rare epilepsies: An essential team effort between biomedical scientists, geneticists and epileptologists.
European Journal of Medical Genetics
, 65
(7)
, Article 104531. 10.1016/j.ejmg.2022.104531.
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Abstract
In the last few years, with the advent of next generation sequencing (NGS), our knowledge of genes associated with monogenic epilepsies has significantly improved. NGS is also a powerful diagnostic tool for patients with epilepsy, through gene panels, exomes and genomes. This has improved diagnostic yield, reducing the time between the first seizure and a definitive molecular diagnosis. However, these developments have also increased the complexity of data interpretation, due to the large number of variants identified in a given patient and due to the phenotypic variability associated with many of the epilepsy-related genes. In this paper, we present examples of variant classification in “real life” clinic situations. We emphasize the importance of accurate phenotyping of the epilepsies including recognising variable/milder phenotypes and expansion of previously described phenotypes. There are some important issues specific to rare epilepsies – mosaicism and reduced penetrance - which affect genetic counselling. These challenges may be overcome through multidisciplinary meetings including epileptologists, pediatric neurologists, and clinical and molecular geneticists, in which every specialist learns from the others in a process which leads to for rapid and accurate diagnosis. This is an important milestone to achieve as targeted therapiesbased on the functional effects of pathogenic variants become available.
| Type: | Article |
|---|---|
| Title: | Defining causal variants in rare epilepsies: An essential team effort between biomedical scientists, geneticists and epileptologists |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ejmg.2022.104531 |
| Publisher version: | https://doi.org/10.1016/j.ejmg.2022.104531 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Epilepsy, Gene, Phenotype, Genotype, Multidisciplinary meetings |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10149577 |
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