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.

中文翻译：

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全外显子组测序可确定与Snyder-Robinson综合征相关的精胺合酶基因（SMS）中的新突变。

据报道，精胺合酶基因（SMS）中功能突变的丧失会导致罕见的X连锁智力障碍，即Snyder-Robinson综合征（SRS）。除了智力障碍，SRS还具有降低骨密度，骨质疏松和面部畸形的特征。SRS表型随着年龄的增长从童年到成年。进行整个外显子组测序以了解致病基因/致病变异。后来我们通过Sanger测序证实了病原体变异。此外，我们还通过HOPE SERVER和SWISS-MODEL进行了突变分析。此外，还为受影响的个体获得了X光片，以确认疾病特征。在本文中，我们报告了由三个SRS和SMS基因中新的错义病原体变异患者组成的第一个巴基斯坦家庭（c.905 C> T p。（Ser302Leu））。除典型的表型外，一名患者还出现了早期发作。临床特征，遗传和计算机分析表明，该家族的患病患者与Snyder-Robinson有关联，并表明该新突变影响了精胺合成酶的活性。SMS中一种新颖的错义变体，c.905C> T p。（Ser302Leu），引起巴基斯坦家族三名成员的斯奈德-罗宾逊综合症（SRS）。