Analysis of the clinical presentation and genetic profile of epilepsy-aphasia spectrum due to GRIN2A gene mutations
Objective To explore the clinical phenotypic features and genetic variation characteristics of children with epilepsy-aphasia spectrum due to GRIN2A gene variants confirmed by second-generation sequencing.Methods The clinical data of 5 children with epilepsy-aphasia spectrum with epileptic onset diagnosed in the Department of Neurology,Children's Hospital Affiliated to Zhengzhou University,from February 2019 to November 2022 were retrospectively analyzed.Whole-exome genome sequencing of the probands using a second-generation sequencing method confirmed that all 5 cases were children with the GRIN2A gene variant.The characteristics of the GRIN2A gene variants were analyzed.Results Among the 5 children diagnosed with epileptic aphasia spectrum due to GRIN2A gene variants,the male-to-female ratio was 4∶1,and the age range of onset was 1.5-4.4 years.The clinical phenotype included seizures in all cases,language and intellectual developmental deficits in 4 cases,and attention deficit hyperactivity disorder in 3 cases.The seizures were manifested as focal seizures or secondary generalized seizures,and were effectively controlled with antiepileptic drugs.Among the 5 children,gene variant of case 1 was originated from a paternal heterozygous variant,and cases 2-5 had de novo variants,which were c.2107C＞T(p.Gln703*)nonsense variant,c.2284G＞A(p.Gly762Arg)missense variant,c.2197del(p.Ala733Glnfs*3)shifted coding variant,c.2511G＞A(p.Trp837*)nonsense variant,and c.1651+1G＞C shear site variant,respectively.None of the 5 loci were reported in the literature.Conclusions Epilepsy-aphasia spectrum is an epilepsy syndrome with a complex onset,and may have different phenotypes at different genetic variant loci,with focal seizures or secondary generalized seizures,which can be effectively controlled with anti-seizure medication.The GRIN2A gene variant is the genetic etiology of the epileptic aphasia spectrum.
GRIN2A geneEpilepsyEpileptic-aphasia spectrumDe novo variants
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万方数据
