Progress in Understanding and Treating SCN2A-Mediated Disorders

Stephan J. Sanders; Arthur J. Campbell; Jeffrey R. Cottrell; Rikke S. Moller; Florence F. Wagner; Angie L. Auldridge; Raphael A. Bernier; William A. Catterall; Wendy K. Chung; James R. Empfield; Alfred L. George; Joerg F. Hipp; Omar Khwaja; Evangelos Kiskinis; Dennis Lal; Dheeraj Malhotra; John J. Millichap; Thomas S. Otis; Steven Petrou; Geoffrey Pitt; Leah F. Schust; Cora M. Taylor; Jennifer Tjernagel; John E. Spiro; Kevin J. Bender

doi:10.1016/j.tins.2018.03.011

Progress in Understanding and Treating SCN2A-Mediated Disorders

Stephan J. Sanders^*, Arthur J. Campbell, Jeffrey R. Cottrell, Rikke S. Moller, Florence F. Wagner, Angie L. Auldridge, Raphael A. Bernier, William A. Catterall, Wendy K. Chung, James R. Empfield, Alfred L. George, Joerg F. Hipp, Omar Khwaja, Evangelos Kiskinis, Dennis Lal, Dheeraj Malhotra, John J. Millichap, Thomas S. Otis, Steven Petrou, Geoffrey PittLeah F. Schust, Cora M. Taylor, Jennifer Tjernagel, John E. Spiro, Kevin J. Bender

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

229 Scopus citations

Abstract

Advances in gene discovery for neurodevelopmental disorders have identified SCN2A dysfunction as a leading cause of infantile seizures, autism spectrum disorder, and intellectual disability. SCN2A encodes the neuronal sodium channel Na_V1.2. Functional assays demonstrate strong correlation between genotype and phenotype. This insight can help guide therapeutic decisions and raises the possibility that ligands that selectively enhance or diminish channel function may improve symptoms. The well-defined function of sodium channels makes SCN2A an important test case for investigating the neurobiology of neurodevelopmental disorders more generally. Here, we discuss the progress made, through the concerted efforts of a diverse group of academic and industry scientists as well as policy advocates, in understanding and treating SCN2A-related disorders.

Original language	English (US)
Pages (from-to)	442-456
Number of pages	15
Journal	Trends in Neurosciences
Volume	41
Issue number	7
DOIs	https://doi.org/10.1016/j.tins.2018.03.011
State	Published - Jul 2018

Funding

This work was supported by grants from the Simons Foundation (SFARI No. 402281, S.J.S.; No. 513133, K.J.B.; No. 491201, A.L.G.; No. 349984, G.P.), the NIH (NIMH No. 100047, R.A.B.), and the Stanley Center for Psychiatric Research at the Broad Institute (A.J.C., J.R.C., D.L., and F.F.W.). We thank Markus Wolff and Katrine Johannesen for their help in combining the lists of published SCN2A variants (Table S1). This work was supported by grants from the Simons Foundation (SFARI No. 402281 , S.J.S.; No. 513133 , K.J.B.; No. 491201 , A.L.G.; No. 349984 , G.P.), the NIH (NIMH No. 100047 , R.A.B.), and the Stanley Center for Psychiatric Research at the Broad Institute (A.J.C., J.R.C., D.L., and F.F.W.). We thank Markus Wolff and Katrine Johannesen for their help in combining the lists of published SCN2A variants (Table S1).

Keywords

Na1.2
autism spectrum disorder
developmental delay
epilepsy
intellectual disability
neurodevelopment
neurodevelopmental disorder
sodium channel

ASJC Scopus subject areas

General Neuroscience

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Sanders, S. J., Campbell, A. J., Cottrell, J. R., Moller, R. S., Wagner, F. F., Auldridge, A. L., Bernier, R. A., Catterall, W. A., Chung, W. K., Empfield, J. R., George, A. L., Hipp, J. F., Khwaja, O., Kiskinis, E., Lal, D., Malhotra, D., Millichap, J. J., Otis, T. S., Petrou, S., ... Bender, K. J. (2018). Progress in Understanding and Treating SCN2A-Mediated Disorders. Trends in Neurosciences, 41(7), 442-456. https://doi.org/10.1016/j.tins.2018.03.011

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abstract = "Advances in gene discovery for neurodevelopmental disorders have identified SCN2A dysfunction as a leading cause of infantile seizures, autism spectrum disorder, and intellectual disability. SCN2A encodes the neuronal sodium channel NaV1.2. Functional assays demonstrate strong correlation between genotype and phenotype. This insight can help guide therapeutic decisions and raises the possibility that ligands that selectively enhance or diminish channel function may improve symptoms. The well-defined function of sodium channels makes SCN2A an important test case for investigating the neurobiology of neurodevelopmental disorders more generally. Here, we discuss the progress made, through the concerted efforts of a diverse group of academic and industry scientists as well as policy advocates, in understanding and treating SCN2A-related disorders.",

keywords = "Na1.2, autism spectrum disorder, developmental delay, epilepsy, intellectual disability, neurodevelopment, neurodevelopmental disorder, sodium channel",

author = "Sanders, \{Stephan J.\} and Campbell, \{Arthur J.\} and Cottrell, \{Jeffrey R.\} and Moller, \{Rikke S.\} and Wagner, \{Florence F.\} and Auldridge, \{Angie L.\} and Bernier, \{Raphael A.\} and Catterall, \{William A.\} and Chung, \{Wendy K.\} and Empfield, \{James R.\} and George, \{Alfred L.\} and Hipp, \{Joerg F.\} and Omar Khwaja and Evangelos Kiskinis and Dennis Lal and Dheeraj Malhotra and Millichap, \{John J.\} and Otis, \{Thomas S.\} and Steven Petrou and Geoffrey Pitt and Schust, \{Leah F.\} and Taylor, \{Cora M.\} and Jennifer Tjernagel and Spiro, \{John E.\} and Bender, \{Kevin J.\}",

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year = "2018",

month = jul,

doi = "10.1016/j.tins.2018.03.011",

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Sanders, SJ, Campbell, AJ, Cottrell, JR, Moller, RS, Wagner, FF, Auldridge, AL, Bernier, RA, Catterall, WA, Chung, WK, Empfield, JR, George, AL, Hipp, JF, Khwaja, O, Kiskinis, E, Lal, D, Malhotra, D, Millichap, JJ, Otis, TS, Petrou, S, Pitt, G, Schust, LF, Taylor, CM, Tjernagel, J, Spiro, JE & Bender, KJ 2018, 'Progress in Understanding and Treating SCN2A-Mediated Disorders', Trends in Neurosciences, vol. 41, no. 7, pp. 442-456. https://doi.org/10.1016/j.tins.2018.03.011

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AU - Sanders, Stephan J.

AU - Campbell, Arthur J.

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AU - Auldridge, Angie L.

AU - Bernier, Raphael A.

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AU - George, Alfred L.

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AU - Khwaja, Omar

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AU - Lal, Dennis

AU - Malhotra, Dheeraj

AU - Millichap, John J.

AU - Otis, Thomas S.

AU - Petrou, Steven

AU - Pitt, Geoffrey

AU - Schust, Leah F.

AU - Taylor, Cora M.

AU - Tjernagel, Jennifer

AU - Spiro, John E.

AU - Bender, Kevin J.

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N2 - Advances in gene discovery for neurodevelopmental disorders have identified SCN2A dysfunction as a leading cause of infantile seizures, autism spectrum disorder, and intellectual disability. SCN2A encodes the neuronal sodium channel NaV1.2. Functional assays demonstrate strong correlation between genotype and phenotype. This insight can help guide therapeutic decisions and raises the possibility that ligands that selectively enhance or diminish channel function may improve symptoms. The well-defined function of sodium channels makes SCN2A an important test case for investigating the neurobiology of neurodevelopmental disorders more generally. Here, we discuss the progress made, through the concerted efforts of a diverse group of academic and industry scientists as well as policy advocates, in understanding and treating SCN2A-related disorders.

AB - Advances in gene discovery for neurodevelopmental disorders have identified SCN2A dysfunction as a leading cause of infantile seizures, autism spectrum disorder, and intellectual disability. SCN2A encodes the neuronal sodium channel NaV1.2. Functional assays demonstrate strong correlation between genotype and phenotype. This insight can help guide therapeutic decisions and raises the possibility that ligands that selectively enhance or diminish channel function may improve symptoms. The well-defined function of sodium channels makes SCN2A an important test case for investigating the neurobiology of neurodevelopmental disorders more generally. Here, we discuss the progress made, through the concerted efforts of a diverse group of academic and industry scientists as well as policy advocates, in understanding and treating SCN2A-related disorders.

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Progress in Understanding and Treating SCN2A-Mediated Disorders

Abstract

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Keywords

ASJC Scopus subject areas

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