Abstract
BackgroundLoss 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.MethodsWhole 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.ResultsIn 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.ConclusionA novel missense variant in the SMS, c.905C > T p. (Ser302Leu), causing Snyder- Robinson Syndrome (SRS) is reported in three members of Pakistani Family.
Highlights
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)
We report the investigations of a family (SRS1) from Pakistan, segregating SRS in a pattern consistent with X-linked recessive inheritance
We report a missense pathogenic variant in this family and it is the first case reported from Asia
Summary
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). Polyamines are organic compounds having more than two amino groups. At neutral pH, they exist as ammonium derivatives. These are polycations that can interact with negatively charged particles, i.e. DNA, RNA and some negatively charged proteins. Around 10 families, segregating this disorder in 20 patients with 11 mutations, have been identified so far. Other names for this disorder include: X-linked syndromic mental retardation, Snyder-Robinson type; Snyder-Robinson X-linked mental retardation syndrome and spermine synthase deficiency (Genetics Home Reference) [4].
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