Helen V. Firth

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.

Copy Number Variant analysis by exome sequencing is an effective approach to optimize diagnostic yield for developmental disorders, the DDD-Africa study

The paper demonstrates that integrating CNV detection into exome sequencing analysis improves diagnostic yield for developmental disorders in the DDD-Africa cohort by 8.3% without additional costs.

An integrated single cell and spatial omics atlas of human prenatal development

Human Developmental Cell Atlas integrates ~4.6 million cells/nuclei from 4-22 post-conception weeks into 454 refined cell types and maps 114 spatial niches across 6PCW whole-embryo sections.

How do clinician and parent reported data differ? An analysis of similarity and difference in the datasets from a cross-syndrome genetics cohort study(GenROC)

This paper compares parent-reported and clinician-reported phenotypic data in a cross-syndrome genetics cohort, finding differences in content and detail but similar quantities.

Domain-wide Mapping of Peer-reviewed Literature for Genetic Developmental Disorders using Machine Learning and Gene2Phenotype

The paper develops an automated pipeline to map genetic developmental disorder literature to Gene2Phenotype using NLP models, achieving high accuracy and scalability for biocuration.

Investigating the Interplay Between Prematurity and Genetic Variation in the Context of Rare Developmental Disorders

The paper examines how prematurity interacts with genetic variation in rare developmental disorders, finding independent and additive effects on phenotypic severity and identifying genetic contributions to preterm birth risk.

The LMSz method - an automatable scalable approach to constructing gene-specific growth charts in rare disorders.

The paper introduces the LMSz method to construct gene-specific growth charts for rare disorders using z-scores, showing gene-specific centiles and trends in anthropometric data.

Mapping MAVE data for use in human genomics applications

The paper maps MAVE data to human reference sequences to improve variant functional assay utility for genomics applications.

Multiple and novel molecular mechanisms in TUBA1A-related tubulinopathy: insights from deep clinical and neuroradiological phenotyping.

The paper identifies novel TUBA1A variants and shows reduced penetrance of malformations of cortical development in tubulinopathies.

Whole genome sequencing of mutation-negative individuals with Cornelia de Lange Syndrome

This study uses whole genome sequencing to identify causative variants in mutation-negative Cornelia de Lange Syndrome patients, finding novel genes and regulatory regions involved.

Substantial role of rare inherited variation in individuals with developmental disorders

The paper investigates the role of rare inherited coding variants in developmental disorders by analyzing family and case/control data, finding significant burdens of damaging variants and estimating their population attributable risk.

Improving the care of children with GENetic Rare disease: Observational Cohort study (GenROC): a study protocol

This study aims to collect clinical data on children with genetic syndromes to identify growth patterns and developmental profiles, guiding clinical care and diagnosis.

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.

Dissecting the contribution of common variants to risk of rare neurodevelopmental conditions

This study investigates how common genetic variants contribute to risk for rare neurodevelopmental conditions and examines indirect genetic effects through parental non-transmitted alleles.

Curating genomic disease-gene relationships with Gene2Phenotype

The paper describes a structured curation process for the Gene2Phenotype project to systematically evaluate and organize genomic disease-gene relationships.

Detection and characterisation of copy number variants from exome sequencing in the DDD study

The paper evaluates CNV detection from exome sequencing in the DDD study, finding it has higher sensitivity than low-resolution CMA and comparable sensitivity to exon-resolution CMA.

Saturation genome editing of DDX3X clarifies pathogenicity of germline and somatic variation

The paper uses saturation genome editing to assess DDX3X variants' functional impact, identifies pathogenic variants for neurodevelopmental disorders, and develops a classifier outperforming existing tools.

A human embryonic limb cell atlas resolved in space and time

This paper creates a human embryonic limb cell atlas using single-cell and spatial transcriptomics, identifying novel cell populations and developmental patterns.

Towards robust clinical genome interpretation: developing a consistent terminology to characterize disease-gene relationships - allelic requirement, inheritance modes and disease mechanisms

This paper standardizes terminology for describing disease-gene relationships to improve variant classification and genetic test interpretation.

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.

Heterozygous loss-of-function SMC3 variants are associated with variable and incompletely penetrant growth and developmental features

The paper identifies SMC3 loss-of-function variants associated with variable growth and developmental features, including some unexpected phenotypes like bone marrow failure and leukemia.

Federated analysis of the contribution of recessive coding variants to 29,745 developmental disorder patients from diverse populations

The paper quantifies the contribution of recessive coding variants to developmental disorders in diverse populations, identifying novel genes and highlighting challenges in interpreting missense variants.

Investigating the role of common cis-regulatory variants in modifying penetrance of putatively damaging, inherited variants in severe neurodevelopmental disorders

The paper investigates whether common cis-regulatory variants modify the penetrance of rare damaging coding variants in neurodevelopmental disorders using transcriptome-wide association and cis-eQTL analysis.

Detection of mosaic chromosomal alterations in children with severe developmental disorders recruited to the DDD study

The paper identifies mosaic chromosomal alterations in children with developmental disorders using SNP array data from the DDD study, finding that many are tissue-specific and undetectable in blood.

IMPROVE-DD: Integrating Multiple Phenotype Resources Optimises Variant Evaluation in genetically determined Developmental Disorders

IMPROVE-DD integrates multiple phenotype data sources to improve variant evaluation in developmental disorders, showing better diagnostic accuracy and fewer false positives.

Optimising diagnostic yield in highly penetrant genomic disease

The paper reports diagnostic outcomes from a large-scale genomic study of developmental disorders, identifying factors that influence diagnostic success.

Genetic and chemotherapeutic causes of germline hypermutation

The paper identifies genetic and chemotherapeutic causes of germline hypermutation by analyzing genome-wide sequences of families with rare genetic diseases.

The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources

The paper describes the formation of the Gene Curation Coalition to standardize gene-disease validity terminology and create a unified database for curated gene-disease assertions.

Structural mapping of GABRB3 variants reveals genotype-phenotype correlation

The paper analyzes GABRB3 variants in a cohort of 71 individuals to identify genotype-phenotype correlations, finding associations between variant locations and specific clinical features.

Detecting cryptic clinically-relevant structural variation in exome sequencing data increases diagnostic yield for developmental disorders

InDelible detects cryptic structural variants in exome sequencing data, improving diagnostic yield for developmental disorders by identifying variants missed by standard methods.