An iPSC line (FINi003-A) from a male with late-onset developmental and epileptic encephalopathy caused by a heterozygous p.E1211K variant in the SCN2A gene encoding the voltage-gated sodium channel Nav1.2

Dmitry A Ovchinnikov; Sharon Jong; Claire Cuddy; Kelly Dalby; Orrin Devinsky; Saul Mullen; Snezana Maljevic; Steve Petrou

doi:10.1016/j.scr.2024.103367

An iPSC line (FINi003-A) from a male with late-onset developmental and epileptic encephalopathy caused by a heterozygous p.E1211K variant in the SCN2A gene encoding the voltage-gated sodium channel Na_v1.2

Stem Cell Res. 2024 Apr:76:103367. doi: 10.1016/j.scr.2024.103367. Epub 2024 Feb 28.

Authors

Dmitry A Ovchinnikov¹, Sharon Jong¹, Claire Cuddy¹, Kelly Dalby², Orrin Devinsky³, Saul Mullen⁴, Snezana Maljevic⁵, Steve Petrou⁶

Affiliations

¹ The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne 3010 VIC, Australia.
² Praxis Precision Medicines, Cambridge, MA, USA.
³ Department of Neurology, NYU Grossman School of Medicine, New York, NY, USA.
⁴ The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne 3010 VIC, Australia; Departments of Medicine and Paediatrics, The University of Melbourne, Austin Health and Royal Children's Hospital, Murdoch Children's Research Institute, Melbourne, VIC, Australia.
⁵ The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne 3010 VIC, Australia. Electronic address: snezana.maljevic@florey.edu.au.
⁶ The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne 3010 VIC, Australia; Praxis Precision Medicines, Cambridge, MA, USA. Electronic address: steven.petrou@florey.edu.au.

PMID: 38479087
DOI: 10.1016/j.scr.2024.103367

Abstract

Many developmental and epileptic encephalopathies (DEEs) result from variants in cation channel genes. Using mRNA transfection, we generated and characterised an induced pluripotent stem cell (iPSC) line from the fibroblasts of a male late-onset DEE patient carrying a heterozygous missense variant (E1211K) in Na_v1.2(SCN2A) protein. The iPSC line displays features characteristic of the human iPSCs, colony morphology and expression of pluripotency-associated marker genes, ability to produce derivatives of all three embryonic germ layers, and normal karyotype without SNP array-detectable abnormalities. We anticipate that this iPSC line will aid in the modelling and development of precision therapies for this debilitating condition.

MeSH terms

Brain Diseases*
Heterozygote
Humans
Induced Pluripotent Stem Cells* / metabolism
Male
Mutation
Mutation, Missense
NAV1.2 Voltage-Gated Sodium Channel / genetics

Substances

SCN2A protein, human
NAV1.2 Voltage-Gated Sodium Channel