期刊
CLINICAL GENETICS
卷 100, 期 4, 页码 412-429出版社
WILEY
DOI: 10.1111/cge.14023
关键词
antiepileptic drug; autism; bromodomain; comorbidity; EEG; epigenetic; histone H3; 3; seizure
资金
- European Union Programme of the Seventh Framework [602531]
- South London and Maudsley NHS Foundation Trust
- Biomedical Research Centre
- Waterloo Foundation [164-3020]
- National Institute for Health Research [RP-PG-0615-20007]
- Canadian Institutes of Health Research [201503MOP-342469]
- European Union
- National Institutes of Health Research (NIHR) [RP-PG-0615-20007] Funding Source: National Institutes of Health Research (NIHR)
The ZMYND11 gene is implicated in epilepsy, with varying seizure types and prognoses, but consistent neurodevelopmental deficits. There is no precise genotype-phenotype correlation for ZMYND11 variants, which are mostly de novo, and further research may reveal more about the underlying mechanisms.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据