Susan Walker

Using SpliceAI to triage splice-altering variants in 7,220 individuals with rare conditions highlights limitations of the precomputed scores

The paper evaluates precomputed SpliceAI scores for splice-altering variant prioritization in NDD cohorts, finding inaccuracies and providing a tool to improve variant triage.

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.

Brain development mutations in the β-tubulin TUBB result in defective ciliogenesis

The paper identifies a novel TUBB mutation linked to both ciliopathy and tubulinopathy brain features, showing it impairs ciliogenesis by altering microtubule dynamics.

Utility of genome sequencing and group-enrichment to support splice variant interpretation in Marfan syndrome

The paper identifies non-canonical FBN1 splice variants in undiagnosed Marfan syndrome families using genome sequencing and RNA testing, finding 20 candidate variants with significant enrichment in FTAAD cases.

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.

Deciphering the role of germline complex de novo structural variations in rare disorders

This study identifies de novo structural variants in a large cohort of rare disease patients, highlighting their prevalence and potential pathogenicity.

A comparative medical genomics approach may facilitate the interpretation of rare missense variation

The paper compares pathogenicity features of missense variants in non-human livestock to human genomic data, finding higher odds of pathogenic classification in cross-species variants.

Leveraging cancer mutation data to predict the pathogenicity of germline missense variants

This study uses cancer mutation data and machine learning to predict the pathogenicity of germline missense variants, showing strong performance in identifying disease-causing variants.

Clinical application of tumour-in-normal contamination assessment from whole genome sequencing

The paper develops a tool to assess tumour contamination in normal samples using whole-genome sequencing data, finding contamination in various cancer types and highlighting risks to variant calling.

Systematic identification of disease-causing promoter and untranslated region variants in 8,040 undiagnosed individuals with rare disease

This study identifies disease-causing promoter and untranslated region variants in 8,040 undiagnosed rare disease patients using a new framework and finds 12 variants with potential pathogenicity.

A systematic assessment of the impact of rare canonical splice site variants on splicing using functional and in silico methods

The paper assesses the impact of rare canonical splice site variants on splicing using functional and in silico methods, finding that 24% of variants do not cause loss-of-function.

CNTN5-/+ or EHMT2-/+ iPSC-Derived Neurons from Individuals with Autism Develop Hyperactive Neuronal Networks

The paper models ASD-related variants in iPSC-derived neurons and finds hyperactive neuronal networks in CNTN5-/+ and EHMT2-/+ lines.

Complete Disruption of Autism-Susceptibility Genes by Gene-Editing Predominantly Reduces Functional Connectivity of Isogenic Human Neurons

This study uses CRISPR to knockout 10 ASD-related genes in iPSCs, revealing reduced functional connectivity in neurons despite diverse gene functions.