Helger G. Yntema

Incompletely penetrant protein-truncating variants confer developmental disorder risk through partial reductions in gene expression

The paper shows inherited protein-truncating variants contribute to developmental disorders through partial gene expression loss, affecting ~20% of children with such variants.

Distinct mechanisms of CNV formation at the human 15q13.3 locus

The paper identifies distinct mechanisms of CNV formation at the human 15q13.3 locus, showing that non-allelic homologous recombination is the primary mechanism, influenced by inversion polymorphisms and population-specific susceptibility.

Genome sequencing reveals novel pathogenic deep-intronic PCDH15 variants, amenable to antisense oligonucleotide-based splice correction

The paper identifies two novel deep-intronic PCDH15 variants in Usher syndrome patients and demonstrates the efficacy of antisense oligonucleotides in correcting their splicing defects.

Clinical long-read genome sequencing for rare disease diagnostics

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

HiFi long-read genomes for difficult-to-detect clinically relevant variants

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.

Clinical exome sequencing data from patients with inborn errors of immunity: cohort level meta-analysis and the benefit of systematic reanalysis

This study reanalyzes exome sequencing data from 1,300 IEI patients, finding that systematic reanalysis increases the molecular diagnostic yield from 11.8% to 15.2%.

Genome sequencing as a generic diagnostic strategy for rare disease

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.

DeNovoCNN: A deep learning approach to de novo variant calling in next generation sequencing data

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

Systematic analysis of short tandem repeats in 38,095 exomes provides an additional diagnostic yield

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

The landscape of autosomal-recessive pathogenic variants in European populations reveals phenotype-specific effects

The paper estimates carrier rates and risk of severe autosomal recessive disorders in European populations using exome sequences.

A RIPOR2 in-frame deletion is a frequent and highly penetrant cause of adult-onset hearing loss

The paper identifies an in-frame deletion in RIPOR2 as a frequent and highly penetrant cause of adult-onset hearing loss, with implications for genetic therapy.

Integrating healthcare and research genetic data empowers the discovery of 28 novel developmental disorders

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

Exome-wide assessment of the functional impact and pathogenicity of multi-nucleotide mutations

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

Meta-analysis of 2,104 trios provides support for 10 novel candidate genes for intellectual disability

This study identifies 10 novel candidate genes for intellectual disability through a meta-analysis of de novo mutations from 2,104 trios.