Lisenka E.L.M. Vissers

The paper shows that SYNGAP1 splice-switching therapy may be ineffective in mature neurons due to reduced A3SS transcript abundance.

This study evaluates long-read genome sequencing in rare disease diagnostics, finding high concordance with standard-of-care tests and incremental diagnostic benefits.

The paper presents a standardized RNA-seq analysis framework for rare disease diagnosis, identifying molecular diagnoses in 7.7% of previously undiagnosed cases.

The paper maps NMD-coupled alternative splicing events in iPSC-derived brain cells and identifies therapeutic targets for neurodevelopmental disorders.

This study uses optical genome mapping to identify de novo and rare inherited structural variants in 57 patient-parent trios, finding 13 de novo SVs and 11 rare inherited SVs, some of which are pathogenic or candidate disease-causing.

The paper identifies monoallelic PSMB8 variants causing impaired immunoproteasome assembly and a novel PRAAS subtype with immunodeficiency.

The paper evaluates the suitability of antisense oligonucleotide therapy for neurodevelopmental disorders by analyzing genetic and phenotypic characteristics, identifying 38% of disorders as potentially targetable.

The paper develops Paraphase, a HiFi-based method to resolve highly similar paralogous genes, revealing genetic diversity and de novo events in segmental duplications.

The paper demonstrates that HiFi long-read sequencing can detect 93% of clinically relevant variants challenging to identify with short-read sequencing, using 30x coverage and showing potential for cost-effective diagnostic implementation.

The paper reanalyzes exome sequencing data from rare disease cases to identify previously undetected copy number variants, resulting in diagnoses for 51 families and partial explanations for 34 individuals.

This paper introduces a whole genome sequencing-based haplarithmisis method for preimplantation genetic testing, improving coverage, reducing artifacts, and enabling new applications like trio-based aneuploidy detection.

The paper uses HiFi long-read sequencing to identify genetic variants in undiagnosed rare disease families, finding novel diagnoses in 13% of cases and candidate variants in 4.3%.

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

The paper identifies variant-specific effects of AFF3 on transcriptome profiles through analysis of patient cohorts and zebrafish models, showing distinct pathophysiological mechanisms for different types of AFF3 variants.

PhenomAD-NDD aggregates comorbid phenotypic data from 51,227 pediatric NDD individuals to identify enriched symptoms and improve clinical understanding.

This study evaluates genome sequencing as a primary diagnostic tool for rare diseases, finding it can detect 95% of clinically relevant variants with a 0.3% false negative rate.

The paper identifies function-altering de novo mutations in neurodevelopmental disorders by analyzing mutational hotspots across homologous protein domains.

PhenoScore quantifies phenotypic similarity using AI and HPO data to improve genetic variant interpretation and genotype-phenotype studies.

This paper compares three facial feature extraction methods for diagnosing genetic disorders, finding that VGGFace2 provides the best performance with 0.78 accuracy.

This study identifies ANKRD11 missense variants as a cause of KBG syndrome by impairing protein stability or transcriptional activity, supporting haploinsufficiency as the underlying mechanism.

DeNovoCNN is a deep learning tool for de novo variant calling in sequencing data, achieving high recall and precision compared to existing methods.

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.

The paper identifies de novo mutations as a significant genetic cause of male infertility, finding several candidate genes and an enrichment of loss-of-function and missense mutations in intolerant genes.

This study systematically analyzes short tandem repeats in exomes to improve diagnostic yield in genetic testing.

The paper identifies mutation-specific pathophysiological mechanisms in SATB1 variants causing distinct neurodevelopmental disorders.

The paper integrates healthcare and research exome sequences to identify 28 novel developmental disorder-associated genes using a simulation-based statistical test.

The paper identifies 299 new genes associated with developmental disorders using exome data from 31,058 trios and finds many more likely remain undiscovered.

This paper systematically reviews and assesses the clinical validity of genes linked to human male infertility, identifying 67 confidently linked genes across 81 phenotypes.

The paper identifies de novo epigenetic variations in congenital disorders and shows their impact on gene expression and potential diagnostic relevance.

The paper evaluates long indel detection in exome sequencing data from intellectual disability patients, identifying three pathogenic indels and highlighting the importance of accurate variant calling.