Vijay S Ganesh

Systematic evaluation of incomplete penetrance in 4,325 rare disease families reveals divergent transcriptional networks in CHD8 pathology

The paper evaluates incomplete penetrance in 4,325 rare disease families, finding 1.6% of diagnosed cases involve inherited variants from unaffected parents and showing divergent transcriptional effects in CHD8-related cases.

Genomic Research as a Critical Pathway to Diagnosis for Individuals with Rare Disease

The Rare Genomes Project provides remote genomic sequencing to rare disease families, achieving a 23.3% diagnostic solve rate and highlighting the role of research in overcoming clinical diagnostic barriers.

Analysis of spliceosome-related coding and noncoding genes and pseudogenes reveals novel candidates

The paper identifies novel spliceosome-related genes and pseudogenes associated with rare diseases using variant analysis and prioritization methods.

Structural variant discovery and diagnostic impact in rare diseases from short-read and long-read sequencing

This study evaluates the diagnostic yield of short-read and long-read sequencing in rare diseases, finding limited added value from long-read sequencing despite increased variant discovery.

Building an Interoperable Rare Disease Multi-omic Resource: The GREGoR Data Model and Dataset

The paper introduces a data model and dataset for rare disease research, enabling interoperable multi-omic data integration across clinical sites.

Benchmarking RNA-seq Tools for Real-World Diagnostic Applications

This study benchmarks RNA-seq tools for diagnostic applications, finding they identify 28 diagnoses from 68 samples but only 9 out of 74 undiagnosed cases.

Transcriptome-wide outlier approach identifies individuals with minor spliceopathies

The paper identifies individuals with minor spliceopathies by analyzing transcriptome-wide splicing outliers in RNA-seq data from rare disease cohorts.

Mitochondrial DNA variant detection in over 6,500 rare disease families by the systematic analysis of exome and genome sequencing data resolves undiagnosed cases

The paper identifies mitochondrial DNA variants in undiagnosed rare disease families using exome and genome sequencing data, leading to diagnoses in 0.4% of cases.

Diagnosing missed cases of spinal muscular atrophy in genome, exome, and panel sequencing datasets

The paper develops and validates SMA Finder, a tool to diagnose spinal muscular atrophy in genome, exome, and panel sequencing data, identifying known and novel cases with high accuracy.

Expert Panel Curation of 31 Genes in Relation to Limb Girdle Muscular Dystrophy

The paper curates 31 genes associated with limb girdle muscular dystrophy (LGMD) using an expert panel and clinical validity framework, identifying 35 gene-disease relationships with varying levels of evidence.

De novo variants in the non-coding spliceosomal snRNA gene RNU4-2 are a frequent cause of syndromic neurodevelopmental disorders

Mostly de novo variants in an 18 bp constrained region of U4 snRNA gene RNU4-2 cause a syndromic neurodevelopmental disorder, estimated to explain 0.41% of cases.

Considerations for reporting variants in novel candidate genes identified during clinical genomic testing

The paper develops criteria for identifying, sharing, and reporting novel candidate genes in clinical genomic testing to improve diagnostic yield for Mendelian conditions.

Novel syndromic neurodevelopmental disorder caused by de novo deletion of CHASERR, a long noncoding RNA

The paper identifies a novel neurodevelopmental disorder caused by de novo deletion of the lncRNA CHASERR, showing its role in regulating CHD2 expression and causing developmental and epileptic encephalopathy.

Rare ACTN2 Frameshift Variants Resulting in Protein Extension Cause Distal Myopathy and Hypertrophic Cardiomyopathy through Protein Aggregation

The paper investigates ACTN2 variants causing distal myopathy and hypertrophic cardiomyopathy, finding that frameshift variants leading to protein extension cause aggregation, while missense variants do not.

Identification of a de novo mutation in TLK1 associated with a neurodevelopmental disorder and immunodeficiency

The paper identifies a de novo TLK1 mutation linked to neurodevelopmental disorder and immunodeficiency, showing impaired kinase activity and altered cytokine responses.

Enhanced virus detection and metagenomic sequencing in patients with meningitis and encephalitis

This study uses metagenomic sequencing to detect pathogens in CNS infections, identifying novel pathogens and improving detection methods.