ZMYND11 variants are a novel cause of centrotemporal and generalised epilepsies with neurodevelopmental disorder
| Autor: | Sophie Bayley, Diana Le Duc, Richard Rosch, Matthew R.G. Taylor, Jens Erik Klint Nielsen, Joanna Kennedy, Stephanie Oates, Charlotte Brasch-Andersen, Lina Quteineh, Katrina M. Allis, Bitten Schönewolf-Greulich, Deb K. Pal, Jennifer Baulcomb, Karen Low, Michael Absoud, Georgia Vasileiou, Christian Korff, T. Michael Yates, M. Albert Basson, Rikke S. Møller, Pernille Mathiesen Tørring, Christiane Zweier, Meena Balasubramanian, Sushma Goyal, Maximilian Radtke, Bernt Popp, Amy Riddett, Gitte Rønde, Bert Callewaert, Zeynep Tümer, Emily Todd, Ulrike Hüffmeier, Amelle Shillington, Renkui Bai, Annemarie Sims |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Databases Factual Cell Cycle Proteins Bioinformatics Epilepsy 0302 clinical medicine Neurodevelopmental disorder antiepileptic drug Intellectual disability bromodomain EEG Child Genetics (clinical) Exome sequencing 0303 health sciences Electroencephalography Microdeletion syndrome Middle Aged 3. Good health DNA-Binding Proteins comorbidity Phenotype Child Preschool Medical genetics Epilepsy Generalized Female Co-Repressor Proteins epigenetic Adult medicine.medical_specialty Adolescent Genotype seizure autism histone H3.3 03 medical and health sciences Young Adult Genetics medicine Humans Genetic Predisposition to Disease Genetic Testing Alleles Genetic Association Studies 030304 developmental biology business.industry Genetic Variation medicine.disease Comorbidity Amino Acid Substitution Neurodevelopmental Disorders Mutation Autism business 030217 neurology & neurosurgery |
| Zdroj: | Oates, S, Absoud, M, Goyal, S, Bayley, S, Baulcomb, J, Sims, A, Riddett, A, Allis, K, Brasch-Andersen, C, Balasubramanian, M, Bai, R, Callewaert, B, Hüffmeier, U, Le Duc, D, Radtke, M, Korff, C, Kennedy, J, Low, K, Møller, R S, Nielsen, J E K, Popp, B, Quteineh, L, Rønde, G, Schönewolf-Greulich, B, Shillington, A, Taylor, M R G, Todd, E, Torring, P M, DMSc, Z T M D P D, Vasileiou, G, Yates, T M, Zweier, C, Rosch, R, Basson, M A & Pal, D K 2021, ' ZMYND11 variants are a novel cause of centrotemporal and generalised epilepsies with neurodevelopmental disorder ', Clinical Genetics, vol. 100, no. 4, pp. 412-429 . https://doi.org/10.1111/cge.14023 |
| ISSN: | 1399-0004 0009-9163 |
| Popis: | 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.\ud \ud \ud We obtained clinical descriptions of sixteen 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.\ud \ud \ud 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.\ud \ud \ud 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. |
| Databáze: | OpenAIRE |
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