Background The SLC2A1 gene plays a vital role in brain energy metabolism.SLC2A1 variants have been reported to be associated with early-onset refractory seizures.This study aims to explore the association between the ...Background The SLC2A1 gene plays a vital role in brain energy metabolism.SLC2A1 variants have been reported to be associated with early-onset refractory seizures.This study aims to explore the association between the SLC2A1 gene and late-onset epilepsy.Methods Trios-based whole-exome sequencing was performed on patients with epilepsy without acquired etiologies.The pathogenicity of the variants was assessed according to the American College of Medical Genetics and Genomics(ACMG)guidelines.Results A total of 14 heterozygous SLC2A1 variants were identifed in 16 unrelated families.The variants were evaluated as“pathogenic”or“likely pathogenic”according to the ACMG guidelines.Ten cases(62.5%)presented with infantile onset seizures and developmental delay/intellectual disability and were diagnosed with developmental and epileptic encephalopathy(DEE).The other six cases(37.5%)exhibited late-onset seizures and normal development.They were diagnosed with idiopathic partial epilepsy(n=2)or idiopathic generalized epilepsy(n=4).Further analysis showed that DEE-associated variants tended to cluster in the transmembrane region,whereas the mild epilepsyassociated variants tended to locate in regions outside the transmembrane region,suggesting a potential molecular sub-regional efect.A total of 15 cases had delayed diagnosis,with the longest delay being 22 years.The SLC2A1 expression stage,which is expressed at relatively high level throughout the whole life span,from the embryonic to adult stages with two peaks at approximately four and 14 years,is generally consistent with the seizure onset age.In addition,patients with early-onset age had variants that were potentially associated with severe damage,suggesting a potential correlation between the age of disease onset and the damaging efects of the variants.Conclusions SLC2A1 variants are associated with late-onset epilepsy,which is consistent with the genetic-dependent stage feature of SLC2A1.Early genetic diagnosis is important for treatment of patients with SLC2A1 variants.展开更多
基金supported by the National Natural Science Foundation of China(82271505 to W.L.)UCB Pharma Ltd.and the Joint Science Research Foundation of China Association Against Epilepsy(CU-2024-042 to B.L.).
文摘Background The SLC2A1 gene plays a vital role in brain energy metabolism.SLC2A1 variants have been reported to be associated with early-onset refractory seizures.This study aims to explore the association between the SLC2A1 gene and late-onset epilepsy.Methods Trios-based whole-exome sequencing was performed on patients with epilepsy without acquired etiologies.The pathogenicity of the variants was assessed according to the American College of Medical Genetics and Genomics(ACMG)guidelines.Results A total of 14 heterozygous SLC2A1 variants were identifed in 16 unrelated families.The variants were evaluated as“pathogenic”or“likely pathogenic”according to the ACMG guidelines.Ten cases(62.5%)presented with infantile onset seizures and developmental delay/intellectual disability and were diagnosed with developmental and epileptic encephalopathy(DEE).The other six cases(37.5%)exhibited late-onset seizures and normal development.They were diagnosed with idiopathic partial epilepsy(n=2)or idiopathic generalized epilepsy(n=4).Further analysis showed that DEE-associated variants tended to cluster in the transmembrane region,whereas the mild epilepsyassociated variants tended to locate in regions outside the transmembrane region,suggesting a potential molecular sub-regional efect.A total of 15 cases had delayed diagnosis,with the longest delay being 22 years.The SLC2A1 expression stage,which is expressed at relatively high level throughout the whole life span,from the embryonic to adult stages with two peaks at approximately four and 14 years,is generally consistent with the seizure onset age.In addition,patients with early-onset age had variants that were potentially associated with severe damage,suggesting a potential correlation between the age of disease onset and the damaging efects of the variants.Conclusions SLC2A1 variants are associated with late-onset epilepsy,which is consistent with the genetic-dependent stage feature of SLC2A1.Early genetic diagnosis is important for treatment of patients with SLC2A1 variants.
