Analysis of the clinical presentation and genetic profile of epilepsy-aphasia spectrum due to GRIN2A gene mutations / 中华神经科杂志

ABSTRACT

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.