Whole-exome sequencing identifies a novel mutation in spermine synthase gene (SMS) associated with Snyder-Robinson Syndrome

• Published in: BMC medical genetics Vol. 21; no. 1; pp. 1 - 168
• Main Authors: Qazi, Talal J, Wu, Qiao, Aierken, Ailikemu, Lu, Daru, Bukhari, Ihtisham, Hussain, Hafiz M. J, Yang, Jingmin, Mir, Asif, Qing, Hong
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 24.08.2020; BioMed Central; BMC
• Subjects: Age; Bone density; Bones; Charged particles; Children; Deoxyribonucleic acid; DNA; DNA sequencing; Families & family life; Fractures; Gait abnormalities; Genes; Genetic analysis; Genetic aspects; Genotype & phenotype; Hydrogen bonds; Intellectual disabilities; Intellectual disability; Mental disorders; Mutation; Osteoporosis; Patients; Phenotypes; Polyamines; Proteins; Radiography; Seizures; Seizures (Medicine); SMS; SMS (Short messaging service); Snyder-Robinson syndrome; Software; Spermine; Spermine synthase; X-linked mental retardation; Islamabad Pakistan; United States > US; Pakistan
• ISSN: 1471-2350; 1471-2350
• DOI: 10.1186/s12881-020-01095-x

Loss of function mutations in the spermine synthase gene (SMS) 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, osteoporosis and facial dysmorphism. SRS phenotypes evolve with age from childhood to adulthood. Whole exome sequencing was performed to know the causative gene/pathogenic variant. Later we confirmed the pathogenic variant 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. In this article, we report the first Pakistani family consisting of three patients with SRS and a novel missense pathogenic variant in the SMS gene (c.905 C > T p.(Ser302Leu)). In addition to the typical phenotypes, one patient presented with early-onset seizures. Clinical features, genetic and in-silico analysis linked the affected patients of the family with Snyder-Robinson and suggest that this novel mutation affects the spermine synthase activity. A novel missense variant in the SMS, c.905C > T p. (Ser302Leu), causing Snyder- Robinson Syndrome (SRS) is reported in three members of Pakistani Family.