Genomic analysis of "microphenotypes" in epilepsy.
Jeavons syndrome
genomics
microphenotype
pediatric status epilepticus
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
22
06
2021
received:
09
04
2021
accepted:
23
07
2021
pubmed:
28
9
2021
medline:
8
4
2022
entrez:
27
9
2021
Statut:
ppublish
Résumé
Large international consortia examining the genomic architecture of the epilepsies focus on large diagnostic subgroupings such as "all focal epilepsy" and "all genetic generalized epilepsy". In addition, phenotypic data are generally entered into these large discovery databases in a unidirectional manner at one point in time only. However, there are many smaller phenotypic subgroupings in epilepsy, many of which may have unique genomic risk factors. Such a subgrouping or "microphenotype" may be defined as an uncommon or rare phenotype that is well recognized by epileptologists and the epilepsy community, and which may or may not be formally recognized within the International League Against Epilepsy classification system. Here we examine the genetic structure of a number of such microphenotypes and report in particular on two interesting clinical phenotypes, Jeavons syndrome and pediatric status epilepticus. Although no single gene reached exome-wide statistical significance to be associated with any of the diagnostic categories, we observe enrichment of rare damaging variants in established epilepsy genes among Landau-Kleffner patients (GRIN2A) and pediatric status epilepticus patients (MECP2, SCN1A, SCN2A, SCN8A).
Identifiants
pubmed: 34569149
doi: 10.1002/ajmg.a.62505
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
138-146Informations de copyright
© 2021 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
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