Johannes R. Lemke

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.

SyMetrics evaluates the pathogenicity of synonymous variants using a machine learning model that integrates multiple predictors, achieving high accuracy in distinguishing deleterious from benign variants.

The paper assesses parental mosaicism in families with de novo variants, finding 4.4% parental mosaicism and proposing amplicon-based sequencing for improved recurrence risk assessment.

This study evaluates the diagnostic yield of monogenic obesity in 521 patients using exome-wide data, finding 5.8% with monogenic obesity and 7.1% with potentially obesogenic variants.

This study identifies de novo KDM2A variants as a cause of a syndromic neurodevelopmental disorder with specific clinical features and functional consequences.

The paper identifies rare genetic variants associated with different epilepsy types, finding the most enrichment in non-acquired focal epilepsy.

The paper identifies STX1A variants causing a neurodevelopmental disorder with or without epilepsy, showing different phenotypes based on variant type.

The paper identifies a novel syndrome caused by the gain-of-function variant p.Glu1099Lys in NSD2, leading to distinct clinical features compared to loss-of-function variants.

The paper identifies biological properties of ion channel residues associated with variant pathogenicity and links them to clinical phenotypes and functional assays.

This study identifies de novo missense variants in SLC32A1 as a cause of a neurodevelopmental disorder with epilepsy, showing they impair GABAergic neurotransmission through two mechanisms.

The paper identifies altered gene expression patterns in 15q13.3 microdeletion carriers, showing dysregulation of genes involved in brain development and contributing to phenotypic variability.

CNV-ClinViewer provides a web tool for clinical interpretation of large copy-number variants by integrating patient and population data with biomedical annotations.

This study shows that loss of Grin2a causes delayed electrophysiological maturation of hippocampal parvalbumin interneurons, leading to transient seizure susceptibility in mice.

The paper analyzes GABRB3 variants in a cohort of 71 individuals to identify genotype-phenotype correlations, finding associations between variant locations and specific clinical features.

This study shows that early exome sequencing in a German cohort of 111 individuals with rare neurodevelopmental disorders reduces diagnostic costs and time by avoiding unnecessary tests.

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

This study describes 20 individuals with de novo SNAP25 variants, identifying intellectual disability and early-onset epilepsy as core symptoms of SNAP25-DEE, with overlaps with other SNARE complex genes.

The paper predicts functional effects of missense variants in voltage-gated sodium and calcium channels using machine learning, achieving high accuracy in distinguishing gain and loss of function variants.

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

The paper analyzes genetic variants in 6,994 individuals with neurodevelopmental disorder with epilepsy to assess diagnostic yield and identify ultra-rare variants in associated genes.

The paper evaluates negative exome sequencing in neurodevelopmental disorders by systematically scoring candidate genes to improve prioritization and validation.

The paper identifies de novo variants in neurodevelopmental disorders with epilepsy and finds associations with specific genes and clinical features.