Alfred L. George

This study shows that suppressing KCNH1 rescues seizures and developmental issues caused by gain-of-function variants in KCNH1.

This paper uses automated patch-clamp assays to reclassify SCN1A missense variants, changing classifications for 50% of tested variants.

The paper investigates functional properties of KCNH1 variants linked to neurodevelopmental disorders, finding most exhibit gain-of-function characteristics.

This study investigates how ATP1A3 dysfunction affects neuronal excitability and development in human neurons linked to alternating hemiplegia of childhood.

This study creates a mouse model of SCN2A-related DEE and shows it exhibits neuronal hyperexcitability, seizure susceptibility, and responsiveness to phenytoin.

This study identifies a uORF in KCNQ2 that represses translation and shows that disrupting it enhances protein expression, with implications for disease and therapy.

This paper uses patient-derived hiPSC-CMs to identify cyproheptadine as a therapeutic for LMNA-related DCM by revealing shared and variant-specific disease mechanisms.

This study examines the impact of a SCN2A pathogenic variant in human neurons using electrophysiology and machine learning, showing that sodium channel blockers can restore normal function.

The paper develops a method combining automated patch clamp and optogenetics to selectively record from specific subtypes of mouse DRG neurons.

The paper introduces Gene Portals, a framework that integrates clinical, functional, and structural data for rare disease variant classification, demonstrating its utility across five gene-specific portals.

The paper investigates four SCN1A variants affecting the same codon, finding mixed and complete loss-of-function effects, suggesting functional diversity beyond codon position.

This study analyzes 42 de novo CACNA1A missense variants in neurodevelopmental disorders, finding most alter channel function and correlate with clinical outcomes.

The paper develops classifiers to distinguish functional and trafficking effects of KCNQ1 variants, improving variant interpretation for LQTS and channelopathies.

This study identifies a small molecule, VU0494372, that enhances KCNQ1 expression and trafficking, offering a potential therapeutic approach for LQTS.

The paper uses machine learning to analyze iPSC-derived neurons from KCNQ2-DEE patients, identifying functional phenotypes and showing retigabine's variable efficacy in rescuing disease features.

This study investigates the distinct roles of NaV1.2 and NaV1.6 in neocortical pyramidal cell excitability using inhibitors and genetic modifications to selectively block each isoform.

The paper investigates the molecular and cellular mechanisms of KCNQ2 encephalopathy through structural analysis, functional assays, and an animal model, revealing multiple pathogenic effects of the G256W variant.

This study creates a new mouse model of AHC with the p.G947R ATP1A3 variant, showing motor dysfunction, seizures, and other neurological traits.

This study examines how alternative splicing and cellular context affect the functional properties of SCN8A variants associated with neurodevelopmental disorders.

The paper develops a Bayesian framework to integrate functional evidence into clinical variant interpretation for epilepsy-related ion channel genes, identifying key parameters that influence pathogenicity classification.

This paper generates a Kcnb1R306C mouse model to study the effects of a voltage-sensing mutation in KCNB1, finding altered neurological and neurobehavioral phenotypes.

This study identifies genetic variants in epilepsy, cardiomyopathy, and arrhythmia genes in a sudden death in the young cohort, finding enrichment of damaging variants and a correlation with younger age at death.

The paper assesses functional properties of SCN2A variants using automated patch clamp recording, revealing complex gain- and loss-of-function patterns beyond a simple binary classification.

This study identifies PRRT2 as a key hub in an epilepsy network disrupted by 16p11.2 duplication and shows its correction rescues multiple neuropsychiatric and seizure-related phenotypes in mice.

This paper investigates the effects of the SCN2A p.K1422E variant in mice, showing mixed functional and behavioral impacts on neurons and neurodevelopmental phenotypes.

This study evaluates 79 KCNQ2 variants using automated patch clamp recording, revealing functional and pharmacological heterogeneity and genotype-dependent retigabine responses.

The paper identifies pathogenic variants in arrhythmia genes in eMERGE-III participants and reclassifies variants of uncertain significance using functional studies.

The paper identifies cryptic prokaryotic promoters causing instability of human NaV channel cDNA in bacteria and presents stabilized plasmids for functional expression.

This paper identifies a KCNB1 pathogenic variant in mice that causes epilepsy and neurobehavioral abnormalities, mimicking human DEE features.