Ingrid Eileen Scheffer

Functional analysis enables reclassification of SCN1A missense variants of uncertain significance in epilepsy

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

Unravelling the genetic basis of stuttering: GWAS meta-analysis highlights link with rare speech disorders

This study conducts a GWAS meta-analysis of stuttering, identifying genetic links with speech disorders and highlighting shared genetic architecture across different ascertainment methods.

Droplet Digital PCR as a First-Line Detection Tool in the Genetic Diagnosis of Vascular Anomalies

The paper evaluates ddPCR as a primary diagnostic tool for vascular anomalies, finding it detects 51% of pathogenic variants in a cohort, with an overall diagnostic yield of 75% when combined with NGS.

Deep tissue sequencing improves genetic diagnostic yield in focal cortical dysplasia

This study uses deep sequencing to identify genetic variants in focal cortical dysplasias, finding pathogenic variants in 71% of cases and highlighting the importance of somatic variants in FCDIIb.

SYNGAP1 haploinsufficiency disrupts early neurodevelopment and accelerates intrinsic neuronal maturation in human patient-derived models

This study investigates SYNGAP1 haploinsufficiency in human patient-derived models, showing disrupted early neurodevelopment and accelerated neuronal maturation.

Knowledge Inclusive Machine Learning for Disease Gene Prioritisation

This paper introduces KIML, a machine learning framework that integrates experimental data with biological knowledge to improve disease gene prioritisation, showing better performance than existing methods.

Genome sequencing boosts diagnostic yield for the developmental and epileptic encephalopathies

Genome sequencing improves diagnostic yield for developmental and epileptic encephalopathies by identifying structural and non-coding variants missed by exome or gene panel testing.

A complex duplication overlapping FBRSL1 implicated in a developmental and epileptic encephalopathy

The paper reports a novel complex structural variant at the FBRSL1 locus causing a dominant-negative mechanism, leading to a severe developmental and epileptic encephalopathy in a patient with additional congenital abnormalities.

Activating Ras-MAPK pathway variants drive hippocampal clonal competition in human epilepsy

This study identifies somatic Ras-MAPK pathway variants in hippocampal tissue from patients with drug-resistant epilepsy, showing their association with clonal competition and worse surgical outcomes.

Transcription factor binding and individual genetic risk for valproate teratogenicity

The paper investigates how genetic variants affecting transcription factor binding contribute to valproate-induced birth defects and identifies EP300 as a key regulator involved in this process.

Cell-type-informed genotyping of mosaic focal epilepsies reveals cell-autonomous and non-cell-autonomous disease-associated transcriptional programs

This study uses snRNA-seq and a new method called GO-TEN to analyze mosaic genetic variants in focal cortical dysplasia, revealing cell-autonomous and non-cell-autonomous transcriptional changes associated with epilepsy.

Scalable automated reanalysis of genomic data in research and clinical rare disease cohorts

The paper develops an automated tool for reanalyzing genomic data in rare disease cohorts, showing improved diagnostic yields through iterative reanalysis.

Pathogenic ultra-rare variants in SLC6A1, SLC6A11, GAD1 and GAD2 are new & recurrent GABAergic loci for GGE syndromes

The paper identifies ultra-rare variants in GABAergic genes associated with genetic generalized epilepsy syndromes and links their functional impact to epilepsy severity.

CONSTITUTIVE OPENING OF THE Kv7.2 PORE ACTIVATION GATE CAUSES KCNQ2-DEVELOPMENTAL ENCEPHALOPATHY

This study identifies two KCNQ2 variants causing developmental encephalopathies by constitutively opening the Kv7.2 pore activation gate, leading to gain-of-function effects.

Diagnostic Utility of Genome-wide DNA Methylation Analysis in Genetically Unsolved Developmental and Epileptic Encephalopathies and Refinement of a CHD2 Episignature

This study evaluates genome-wide DNA methylation analysis in genetically unsolved DEEs, identifying 10 causative or candidate genetic causes and refining a CHD2 episignature.

Emerging neurodevelopmental mechanisms in patient induced pluripotent stem cells-derived spheroids modelling SCN1A Dravet Syndrome

This study uses patient-derived iPSC spheroids to model SCN1A Dravet Syndrome, revealing dysregulated developmental processes and predicting drug response to fenfluramine.

Optical genome mapping enables accurate repeat expansion testing

This study evaluates optical genome mapping (OGM) for detecting STR repeat expansions and somatic instability, showing high accuracy and efficiency compared to current methods.

Atenolol reduces cardiac-mediated mortality in a genetic mouse model of sudden unexpected death in epilepsy

This study shows that atenolol reduces cardiac-related mortality in a genetic mouse model of SUDEP by mitigating seizure and LQTS interactions.

Long-read sequencing and profiling of RNA-binding proteins reveals the pathogenic mechanism of aberrant splicing of an SCN1A poison exon in epilepsy

The paper investigates how SCN1A variants in a poison exon cause aberrant splicing, reduced Nav1.1 protein, and epilepsy through RBP interactions.

Genetic aetiologies for childhood speech disorder: novel pathways co-expressed during brain development

This study identifies 18 high-confidence genetic variants in 26% of childhood apraxia of speech cases, expanding the list of candidate genes and highlighting shared pathways with other neurodevelopmental disorders.

Missense variants in the voltage sensing and pore domain of KCNH5 cause neurodevelopmental phenotypes including epilepsy

The paper reports a cohort of 17 patients with pathogenic KCNH5 variants causing neurodevelopmental disorders and epilepsy, identifying genotype-phenotype correlations.

SETBP1 variants outside the degron disrupt DNA-binding and transcription independent of protein abundance to cause a heterogeneous neurodevelopmental disorder

The paper investigates SETBP1 variants outside the degron, showing they cause a heterogeneous neurodevelopmental disorder through loss-of-function mechanisms independent of protein abundance.

Ultra-rare constrained missense variants in the epilepsies: Shared and specific enrichment patterns in neuronal gene-sets

The paper analyzes ultra-rare variants in epilepsy patients to identify gene-set enrichment patterns and differential impacts in neuronal gene categories.

Genome-wide association study of febrile seizures identifies seven new loci implicating fever response and neuronal excitability genes

This study identifies seven new genetic loci associated with febrile seizures, linking them to fever response and neuronal excitability genes, and suggests potential clinical applications of polygenic risk scores.

Pathogenic MAST3 variants in the STK domain are associated with epilepsy

The paper identifies de novo MAST3 variants in individuals with epilepsy, showing they may confer gain-of-function and are restricted to excitatory neurons in the cortex.

Loss-of-function variants in the cardiac Kv11.1 channel as a genetic biomarker for SUDEP

The paper identifies loss-of-function KCNH2 variants as enriched in SUDEP patients compared to epilepsy controls, suggesting a genetic biomarker for SUDEP risk.

Tracing Autism Traits in Large Multiplex Families to Identify Endophenotypes of the Broader Autism Phenotype

The paper identifies four psychological endophenotypes of the Broader Autism Phenotype using phenotyping in large multiplex families and shows high sensitivity and specificity for BAP classification.

Ultra-rare genetic variation in the epilepsies: a whole-exome sequencing study of 17,606 individuals

This study identifies ultra-rare genetic variants associated with different epilepsy types using whole-exome sequencing in 17,634 individuals.

Abnormal cell sorting underlies the unique X-linked inheritance of PCDH19 Epilepsy

The paper shows that PCDH19 mutations in females cause abnormal cell sorting in the developing cortex, leading to epilepsy, while males are unaffected due to normal sorting.