Clinical and genetic analysis of PACS2 gene variant in two child patients with developmental and epileptic encephalopathy 66 / 中华医学遗传学杂志

ABSTRACT

OBJECTIVE@#To explore the clinical phenotype and genetic characteristics of two children with developmental epileptic encephalopathy type 66.@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the two children and their parents. Whole exome sequencing (WES) was carried out and suspected variant was verified by Sanger sequencing.@*RESULTS@#The main manifestations of the two children were neonatal onset seizures, hypotonia, global developmental delay, and facial dysmorphisms. Cranial MRI showed delayed myelination in case 1 and cerebellar dysgenesis in case 2. WES has identified a de novo pathogenic variant in the PACS2 gene in both patients, namely c.625G>A (p.Glu209Lys)(NM_001100913.3), which was reported as a pathogenic variant before. This variant was predicted to be pathogenic according to the American College of Medical Genetics and Genomics guideline (PS2+PM2+PP3). The seizures were controlled after combination treatment of sodium valproate and levetiracetam in both cases. At last follow-up, the motor and intellectual development of the 2 cases were improved. Compared with the cases reported, the clinical symptoms and signs of our cases were relatively mild, and the treatment effects were fairly good.@*CONCLUSION@#The variant of c.625G>A (p.Glu209Lys) in PACS2 gene is a hotspot variant of developmental epileptic encephalopathy 66. Gene testing can facilitate the clinical diagnosis and treatment.