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

Springer Science and Business Media LLC - Tập 21 - Trang 1-7 - 2020
Talal J. Qazi1, Qiao Wu2, Ailikemu Aierken1, Daru Lu2,3, Ihtisham Bukhari4, Hafiz M. J. Hussain5, Jingmin Yang2,3,6, Asif Mir7, Hong Qing1
1Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing, China
2State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
3Chongqing Population and Family Planning, Science and Technology Research Institute, National Health and Family Planning Commission, Chongqing, China
4Key Laboratory of Helicobacter pylori and Microbiota and GI Cancer in Henan Province, Marshall Medical Research Center of Zhengzhou University, The 5th affiliated Hospital of Zhengzhou University, Zhengzhou, China
5Department of Nephrology, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
6Shanghai WeHealth Biomedical Technology Co., Ltd., Shanghai, China
7Department of Biological Sciences, FBAS, International Islamic University, Islamabad, Pakistan

Tóm tắt

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.

Tài liệu tham khảo

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