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ZMYND11 variants are a novel cause of centrotemporal and generalised epilepsies with neurodevelopmental disorder
Author(s) -
Oates Stephanie,
Absoud Michael,
Goyal Sushma,
Bayley Sophie,
Baulcomb Jennifer,
Sims Annemarie,
Riddett Amy,
Allis Katrina,
BraschAndersen Charlotte,
Balasubramanian Meena,
Bai Renkui,
Callewaert Bert,
Hüffmeier Ulrike,
Le Duc Diana,
Radtke Maximilian,
Korff Christian,
Kennedy Joanna,
Low Karen,
Møller Rikke S.,
Nielsen Jens Erik Klint,
Popp Bernt,
Quteineh Lina,
Rønde Gitte,
SchönewolfGreulich Bitten,
Shillington Amelle,
Taylor Matthew RG,
Todd Emily,
Torring Pernille M.,
Tümer Zeynep,
Vasileiou Georgia,
Yates T. Michael,
Zweier Christiane,
Rosch Richard,
Basson M. Albert,
Pal Deb K.
Publication year - 2021
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.14023
Subject(s) - neuroscience , epilepsy , genetics , neurodevelopmental disorder , medicine , biology , gene
Abstract 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.