Spermine Synthase Deficiency Resulting in X-Linked Intellectual Disability (Snyder–Robinson Syndrome)

Abstract Background: 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. Methods: 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. Results: 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 Conclusion: 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.

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

10.21203/rs.3.rs-23574/v3 ◽

2020 ◽

Author(s):

Talal J. Qazi ◽

Qiao Wu ◽

Ailikemu Aierken ◽

Daru Lu ◽

Ihtisham Bukhari ◽

...

Keyword(s):

Intellectual Disability ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Mutational Analysis ◽

Novel Mutation ◽

Pathogenic Variant ◽

Facial Dysmorphism ◽

Pakistani Family ◽

Spermine Synthase ◽

Whole Exome

Abstract Background: 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. Methods: 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. Results: 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 activityConclusion: 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.

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

10.21203/rs.3.rs-23574/v2 ◽

2020 ◽

Author(s):

Talal J. Qazi ◽

Qiao Wu ◽

Ailikemu Aierken ◽

Daru Lu ◽

Ihtisham Bukhari ◽

...

Keyword(s):

Intellectual Disability ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Mutational Analysis ◽

Novel Mutation ◽

Pathogenic Variant ◽

Facial Dysmorphism ◽

Pakistani Family ◽

Spermine Synthase ◽

Whole Exome

Abstract Background: 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. Methods: 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. Results: 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 activityConclusion: 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.

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

10.21203/rs.3.rs-23574/v1 ◽

2020 ◽

Author(s):

Talal J. Qazi ◽

Qiao Wu ◽

Ailikemu Aierken ◽

Daru Lu ◽

Ihtisham Bukhari ◽

...

Keyword(s):

Intellectual Disability ◽

Exome Sequencing ◽

Missense Mutation ◽

Whole Exome Sequencing ◽

Mutational Analysis ◽

Novel Mutation ◽

Facial Dysmorphism ◽

Clinical Genetic ◽

Spermine Synthase ◽

Whole Exome

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.

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Normocentric biases taint cognitive neuroscience and intervention of autism

Behavioral and Brain Sciences ◽

10.1017/s0140525x18002297 ◽

2019 ◽

Vol 42 ◽

Cited By ~ 1

Author(s):

Laurent Mottron

Keyword(s):

Intellectual Disability ◽

Cognitive Neuroscience ◽

Social Motivation ◽

Repetitive Behaviors ◽

Restricted Interests ◽

Autistic People

Abstract Stepping away from a normocentric understanding of autism goes beyond questioning the supposed lack of social motivation of autistic people. It evokes subversion of the prevalence of intellectual disability even in non-verbal autism. It also challenges the perceived purposelessness of some restricted interests and repetitive behaviors, and instead interprets them as legitimate exploratory and learning-associated manifestations.

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