Lynn S. Pais

The paper identifies rare variants in CSMD2 associated with neurodevelopmental disorders, showing both recessive and dominant inheritance patterns and functional impairments.

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.

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

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 Evidence Aggregator (EvAgg) uses generative AI to streamline rare disease diagnostics by extracting and summarizing genetic variant and clinical information from literature, improving efficiency and accuracy.

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

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

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 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.

The paper identifies three novel candidate genes for ocular congenital cranial dysinnervation disorders using zebrafish CRISPR screening and protein binding microarrays to assess variant functionality.

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 detects and classifies copy number variants in exome data from 6,633 families, identifying causal CNVs in 173 families and improving classification standards.

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.

This study identifies biallelic HMGCS1 variants as a novel cause of rigid spine syndrome, showing hypomorphic effects through functional and clinical analyses.

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

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 identifies six rare de novo missense variants in WDR5 associated with neurodevelopmental disorders and highlights their impact on COMPASS family protein interactions.

The paper shows inherited CHD3 variants cause Snijders Blok-Campeau syndrome with variable expressivity, overlapping with de novo variants' phenotypes, and suggests reduced penetrance is not due to expression compensation.

seqr is a web-based tool for analyzing rare disease genomic data, enabling variant filtering, annotation, and collaboration, with over 10,000 families analyzed and 300 novel disease genes discovered.

The paper identifies pathogenic variants in SMARCA5 as a cause of a neurodevelopmental syndrome with mild facial dysmorphia and developmental delay.

The paper identifies a deep intronic variant in NDUFB10 causing a cryptic exon and isolated Complex I deficiency through RNA sequencing in two affected siblings.

This paper reports on 38 individuals with KMT2E variants, finding that heterozygous variants cause neurodevelopmental disorders, epilepsy, and variable expressivity by sex.