Helen S. Stewart

Biallelic variants in RNU2-2 cause a remarkably frequent developmental epileptic encephalopathy

The paper identifies biallelic variants in RNU2-2 as a frequent cause of a severe developmental epileptic encephalopathy, distinct from a dominant disorder, and links them to reduced U2-2 abundance.

A scalable and equitable framework for target and patient prioritisation in rare disease antisense therapeutics

The paper presents a framework for prioritizing targets and patients for antisense oligonucleotide therapies in rare diseases, focusing on equitable and systematic decision-making.

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.

Large-scale evaluation of outcomes following a genetic diagnosis in children with severe developmental disorders

The paper evaluates clinical outcomes after genetic diagnosis in children with severe developmental disorders, finding that most families received condition-specific information and support.

Genetic association analysis of 269 rare diseases reveals novel aetiologies

This study uses a computational framework to analyze genetic data from 77,539 genomes, identifying 21 novel genetic associations with 269 rare diseases.

The PREGCARE study: Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation

The paper presents a method to assess recurrence risk of de novo mutations in families using deep-sequencing and haplotyping, finding that 59% of DNMs had reduced risk below 0.1%.

Mouse and cellular models of KPTN-related disorder implicate mTOR signalling in cognitive and progressive overgrowth phenotypes

The paper investigates KPTN-related disorder using mouse and human stem cell models, identifying mTOR pathway dysregulation as a key mechanism underlying cognitive and overgrowth phenotypes.

Non-coding variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms

The paper identifies non-coding variants upstream of MEF2C causing severe developmental disorder through three distinct loss-of-function mechanisms, showing their diagnostic importance in existing exome datasets.