DYNC1H1 variants associated with infant-onset epilepsy without neurodevelopmental disorders
DYNC1H1 variants associated with infant-onset epilepsy without neurodevelopmental disorders
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DOI：
10.1016/j.seizure.2023.10.010
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发表时间：
2024-04-05
影响因子：
3
通讯作者：
Meng，Xiang-Hong
中科院分区：
文献类型：
--
作者：
Wu，Wu-Chen;Liang，Xiao-Yu;Meng，Xiang-Hong
ObjectivesTheDYNC1H1variants are associated with abnormal brain morphology and neuromuscular disorders that are accompanied by epilepsy. This study aimed to explore the relationship betweenDYNC1H1variants and epilepsy.Materials and MethodsTrios-based whole-exome sequencing was performed on patients with epilepsy. Previously reported epilepsy-relatedDYNC1H1variants were systematically reviewed to analyse genotype-phenotype correlation.ResultsTheDYNC1H1variants were identified in four unrelated cases of infant-onset epilepsy, including twode novoand two biallelic variants. Two patients harbouringde novomissense variants located in the stem and stalk domains presented with refractory epilepsies, whereas two patients harbouring biallelic variants located in the regions between functional domains had mild epilepsy with infrequent focal seizures and favourable outcomes. One patient presented with pachygyria and neurodevelopmental abnormalities, and the other three patients presented with normal development. These variants have no or low frequencies in the Genome Aggregation Database. All the missense variants were predicted to be damaging using silico tools. Previously reported epilepsy-related variants were monoallelic variants, mainlyde novomissense variants, and all the patients presented with severe epileptic phenotypes or developmental delay and malformations of cortical development. Epilepsy-related variants were clustered in the dimerization and stalk domains, and generalized epilepsy-associated variants were distributed in the stem domain.ConclusionThis study suggested thatDYNC1H1variants are potentially associated with infant-onset epilepsy without neurodevelopmental disorders, expanding the phenotypic spectrum ofDYNC1H1. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic variation.
