Sarah L. Stenton

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.

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.

This study evaluates the diagnostic yield of long-read genome sequencing in cases where short-read sequencing failed, finding an incremental yield of 4.7% due to LR-GS's ability to detect structural variants and other complex genomic features.

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.

The paper presents genetic and phenotypic data from 521 children with neurodevelopmental disorders in Kenya and South Africa, highlighting high genetic diagnosis rates linked to environmental risk factors.

The paper evaluates how well variant effect predictors perform across different genetic ancestries, finding comparable performance across major groups after accounting for allele frequency.

The paper analyzes over 800,000 human genomes to assess penetrance of clinically relevant variants, finding that 95% of pLoF variants in severe diseases have explanations for lack of disease manifestation.

The paper identifies de novo variants in RNU4-2 and RNU5B-1 as causes of neurodevelopmental disorders by disrupting splicing, with variant location and allele phase influencing clinical severity.

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.

The paper calibrates three new computational tools for clinical variant classification, finding they provide evidence strength comparable to previously recommended tools.

This study evaluates the diagnostic yield of long-read nanopore sequencing in rare disease detection, finding it covers more genes and detects additional variants compared to short-read sequencing.

The paper assesses rare missense variants in genome sequences using PP3/BP4 evidence strength classifications and finds few variants meet strong or moderate criteria.

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.

The paper evaluates variant prioritization methods for rare disease diagnosis using data from the Rare Genomes Project, finding that top models identify causal variants in most solved families and uncover potential candidates in unsolved ones.

The paper develops a method to infer compound heterozygosity from exome sequencing data, achieving high accuracy in phasing rare variants for recessive disease diagnosis.

This study evaluates genome sequencing's diagnostic yield in a cohort of undiagnosed rare disease patients, finding it solves 29.3% of cases with specific variant types not detectable by exome sequencing.

The paper implements RNA-seq in diagnostics for Mendelian diseases, achieving a 16% diagnosis rate in WES-inconclusive cases by detecting aberrant expression, splicing, and mono-allelic expression.

This study analyzes 2,023 pediatric exomes to diagnose mitochondrial disease, identifying 1,109 molecular diagnoses and 62 novel disease genes through exome sequencing and functional studies.

Adding tandem mass tag proteomics to genome and transcriptome data resolved 22% of 121 unsolved suspected mitochondrial disease cases and surfaced two new disease genes.