Whole exome sequencing identifies a novel mutation in spermine synthase gene (SMS) associated with Snyder-Robinson Syndrome
Abstract Background: Mutations in the spermine synthase (SMS) gene have been reported to cause a rare x-linked intellectual disability known as Snyder-Robinson Syndrome (SRS). Besides intellectual disability, SRS is also characterized by reduced bone density, bone deformities, osteoporosis and facial dysmorphism. SRS phenotypes evolve with age from childhood to adulthood. Methods: Whole exome sequencing was performed to know the causative gene/mutation. Later we confirmed the mutation through sanger sequencing. Furthermore, we also performed the mutational analysis through HOPE SERVER and SWISS-MODEL. Also, radiographs were also obtained for affected individual to confirm the disease features. Results: In this article, we report the first Pakistani family consisting of three patients with SRS and a novel missense mutation in the SMS gene (c.905C >T: p.S302L). In addition to the typical phenotypes, one patient presented with epilepsy from an early age that was characterized by generalized seizures. The clinical, genetic and in-silico analysis, review of the literature links the affected patients of the family with Snyder-Robinson syndrome and mutation affects the spermine synthase activityConclusion: A novel missense mutation in the SMS gene (c.905C >T: p.S302L) causing Snyder-Robinson Syndrome (SRS) reported in Pakistan Family.