Abstract: Background：SLC6A1 encodes the gammaaminobutyric acid (GABA) transporter protein 1 (GAT1), which is responsible for the reuptake of GABA from the synapse. It plays an important role in the pathogenesis of neurological disorders such as epilepsy, intellectual disability and autism. Objective：To summarize the clinical phenotypes and results of genetic testing in children with SLC6A1 mutations. Design：Case series report. Methods：Patients with SLC6A1 mutations treated in the Department of Neurology, Children's Hospital of Fudan University from December 2007 to October 2021 were enrolled. The clinical data of patients were collected to summarize the clinical manifestations, therapeutic effects and genetic results. The relationship between reported gene variants and clinical phenotypes was summarized through searching databases. Main outcome measures：Mutation sites of SLC6A1 gene and clinical phenotypes. Results：Five children were included in the study, including 4 males and 1 female. They experienced seizure onset from 1 to 3 years old. 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 patients received valproic acid monotherapy, and the other two received valproic acid in combination with levetiracetam. De novo heterozygous SLC6A1 gene mutations were identified in these patients, including 3 missense mutations, 1 splicing mutation and 1 nonsense mutation. Two mutations including c.1379T>G (p.L460R), and c.1485G>A (p.W495X) have not been previously reported in public. Alteration of amino acids of GAT1 caused by pathogenic or likely pathogenic missense variants are largely clustered around the extracellular domain of EC34 and the seventh transmembrane domain. Conclusion：Most of the patients associated with SLC6A1 gene mutations experienced seizure onset in early childhood. The patients presented with various types of seizures. Valproic acid was effective to control seizures. Most of the patients had developmental delays. The discovery of new variants has enriched the spectrum of SLC6A1 gene variants.

Key words: Epilepsy, Developmental delay, Gene, SLC6A1, Valproic acid