Analysis of clinical features and genetic variants among patients with SLC6A1 mutations

Objective: To summarize the clinical features and results of genetic testing in children with SLC6A1 mutations. Methods: The clinical data of patients was collected. Whole exome sequencing (WES) was carried out to screen the potential variants of genomic DNA, and Sanger sequencing was further used to verify the candidate variants. Results: Five patients with de novo heterozygous SLC6A1 gene mutations were identified, including 3 missense mutations, 1 splicing mutation and 1 nonsense mutation. Three mutations have not been previously reported in public database. Among them, 4 had myoclonic seizures，3 cases had absence seizures, 2 cases had myoclonic-atonic seizures, and 1 had generalized tonic clonic seizures. Developmental delay was present in all patients. Delayed language development was prominent. Four of the 5 patients became seizure free. Two of them received valproic acid monotherapy. Two patients were treated with valproic acid in combination with levetiracetam. Conclusions: Most of the patients associated with SLC6A1 gene mutations experienced seizure onset at early childhood. The majority of patients presented with myoclonic seizures, absence seizures, and myoclonic-atonic seizures. Valproic acid was effective to control seizures. Most of the patients had developmental delay. The discovery of new variants has enriched the spectrum of SLC6A1 gene variants.
Keywords: Epilepsy; Developmental delay; Gene; SLC6A1; Valproic acid