ZMYND11 variants are a novel cause of centrotemporal and generalised epilepsies with neurodevelopmental disorder.
Adolescent
Adult
Alleles
Amino Acid Substitution
Cell Cycle Proteins
/ genetics
Child
Child, Preschool
Co-Repressor Proteins
/ genetics
DNA-Binding Proteins
/ genetics
Databases, Factual
Electroencephalography
Epilepsy
/ diagnosis
Epilepsy, Generalized
/ diagnosis
Female
Genetic Association Studies
Genetic Predisposition to Disease
Genetic Testing
Genetic Variation
Genotype
Humans
Male
Middle Aged
Mutation
Neurodevelopmental Disorders
/ diagnosis
Phenotype
Young Adult
EEG
antiepileptic drug
autism
bromodomain
comorbidity
epigenetic
histone H3.3
seizure
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
25
06
2021
received:
17
04
2021
accepted:
30
06
2021
pubmed:
4
7
2021
medline:
1
2
2022
entrez:
3
7
2021
Statut:
ppublish
Résumé
ZMYND11 is the critical gene in chromosome 10p15.3 microdeletion syndrome, a syndromic cause of intellectual disability. The phenotype of ZMYND11 variants has recently been extended to autism and seizures. We expand on the epilepsy phenotype of 20 individuals with pathogenic variants in ZMYND11. We obtained clinical descriptions of 16 new and nine published individuals, plus detailed case history of two children. New individuals were identified through GeneMatcher, ClinVar and the European Network for Therapies in Rare Epilepsy (NETRE). Genetic evaluation was performed using gene panels or exome sequencing; variants were classified using American College of Medical Genetics (ACMG) criteria. Individuals with ZMYND11 associated epilepsy fell into three groups: (i) atypical benign partial epilepsy or idiopathic focal epilepsy (n = 8); (ii) generalised epilepsies/infantile epileptic encephalopathy (n = 4); (iii) unclassified (n = 8). Seizure prognosis ranged from spontaneous remission to drug resistant. Neurodevelopmental deficits were invariable. Dysmorphic features were variable. Variants were distributed across the gene and mostly de novo with no precise genotype-phenotype correlation. ZMYND11 is one of a small group of chromatin reader genes associated in the pathogenesis of epilepsy, and specifically ABPE. More detailed epilepsy descriptions of larger cohorts and functional studies might reveal genotype-phenotype correlation. The epileptogenic mechanism may be linked to interaction with histone H3.3.
Substances chimiques
Cell Cycle Proteins
0
Co-Repressor Proteins
0
DNA-Binding Proteins
0
ZMYND11 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
412-429Subventions
Organisme : CIHR
ID : 201503MOP-342469
Pays : Canada
Organisme : National Institute for Health Research
ID : RP-PG-0615-20007
Organisme : European Union
Organisme : National Institute for Health Research
ID : DKP
Organisme : Medical Research Council
ID : MR/K022377/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N026063/1
Pays : United Kingdom
Organisme : South London and Maudsley NHS Foundation Trust
Organisme : European Union Programme of the Seventh Framework: Development of Strategies for Innovative Research to improve diagnosis, prevention and treatment in children with difficult to treat Epilepsy
ID : 602531
Organisme : Biomedical Research Centre
Organisme : Waterloo Foundation
ID : DKP
Organisme : Waterloo Foundation
ID : 164-3020
Organisme : Wellcome Trust
ID : 209164/Z/17/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V037307/1
Pays : United Kingdom
Organisme : CIHR
ID : DKP
Pays : Canada
Organisme : European Union Programme of the Seventh Framework: Development of Strategies for Innovative Research to improve diagnosis, prevention and treatment in children with difficult to treat Epilepsy
ID : DKP
Informations de copyright
© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.
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