Identification of ARV1 Gene Mutations in Three Pediatric Cases of Developmental and Epileptic Encephalopathy.

The ARV1 gene produces a protein made up of 271 amino acids that helps transport fats across membranes within the cell's endoplasmic reticulum (ER), a key area involved in processing lipids. This protein is related to an enzyme called ACAT2, which is important for managing cholesterol and fat levels in the body. This protein features an N-terminal zinc-binding motif located in the cytosol, followed by multiple domains that span the ER membrane, and concludes with a C-terminus that terminates in the ER lumen. ARV1 deficiency clinically manifests as autosomal recessive developmental and epileptic encephalopathy 38 (DEE38) in humans.  In this report, we share three pediatric cases presenting with early-onset epileptic encephalopathy and significant developmental delay. Whole-exome sequencing (WES) identified two pathogenic ARV1 variants: p.Cys61Tyr (missense) and p.Phe144Argfs5* (frameshift), both predicted to severely disrupt protein structure and function. These findings add to what we know about how mutations in the ARV1 gene can lead to developmental and epileptic encephalopathy (DEE38), and they strengthen our understanding of the gene's role in brain development. The children in our report also show how widely the symptoms of ARV1-related conditions can vary from case to case. Their experiences highlight just how important early genetic testing can be, especially for young patients with unexplained seizures and developmental challenges. Our report contributes to understanding the spectrum of complex neurological conditions. By sharing these cases, we're adding to the growing knowledge about ARV1-related encephalopathies and reinforcing why this gene deserves a place in targeted epilepsy genetic panels.