Related Experiment Video
Updated: Jul 16, 2025
A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
Electroclinical Features in Two Novel STRADA Patients and a Functional Yeast Assay for the Validation of Missense
Caterina Ancora1, Marco Marchi2, Claudia Maria Bonardi1
1Pediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University of Padua, Padua, Italy.
Abstract:
Loss of function of the STRADA gene, an upstream mTOR inhibitor, causes a rare neurodevelopmental disorder characterized by polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE syndrome). Patients display a homogeneous phenotype including early-onset drug-resistant epilepsy, severe psychomotor delay, multisystemic comorbidities, and increased risk of premature death. The administration of sirolimus, an mTOR inhibitor, is helpful in controlling seizures in this syndrome. We report the electroclinical phenotype of two novel patients and the development of a yeast model to validate the pathogenicity of missense variants. Patient 1 harbored a missense STRADA variant and had a peculiar electroclinical phenotype with a relatively mild epilepsy course. Patient 2 harbored a truncating STRADA variant and showed a typical PMSE phenotype and a favorable response to early treatment with sirolimus. When we modeled the p.(Ser264Arg) STRADA change in its yeast homolog SPS1, it impaired SPS1 function. The results underlie the importance of a timely molecular diagnosis in these patients and show that yeast is a simple yet effective model to validate the pathogenicity of missense variants.
