Precision physiology and rescue of brain ion channel disorders

2017/04/20 by Jeffrey Noebels, Jeffrey L. Noebels · 36 citations
Biochemistry, Genetics and Molecular Biology · Medicine · Neuroscience · Psychology · #Autism #Bioinformatics #Biology #Clinical phenotype #Cognition #Computational biology #Disease #Epilepsy #Gene #Genetics #Genomics and Rare Diseases #Internal medicine #Ion channel #Ion channel regulation and function #Medicine #Neuroscience #Phenotype #Psychiatry #Psychology #RNA and protein synthesis mechanisms

paper · pdf · doi:10.1085/jgp.201711759

published in The Journal of General Physiology 149(5), 533-546 (Rockefeller University Press)

openalex publication_date 2017/04/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

Ion channel genes, originally implicated in inherited excitability disorders of muscle and heart, have captured a major role in the molecular diagnosis of central nervous system disease. Their arrival is heralded by neurologists confounded by a broad phenotypic spectrum of early-onset epilepsy, autism, and cognitive impairment with few effective treatments. As detection of rare structural variants in channel subunit proteins becomes routine, it is apparent that primary sequence alone cannot reliably predict clinical severity or pinpoint a therapeutic solution. Future gains in the clinical utility of variants as biomarkers integral to clinical decision making and drug discovery depend on our ability to unravel complex developmental relationships bridging single ion channel structure and human physiology.

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