John Christodoulou

A flexible diet platform for the nutrigenomic screening of Drosophila disease models

The paper develops a flexible diet platform for nutrigenomic screening in Drosophila disease models, showing it can identify nutrient-specific effects on disease phenotypes.

De novo truncation variants in the low-complexity C-terminal region of XRN1 are associated with a dominant form of lethal infantile mitochondrial cardiomyopathy

The paper identifies de novo truncating variants in XRN1's C-terminal region causing lethal infantile mitochondrial cardiomyopathy by disrupting its interaction with EDC4.

Workshops to improve use of functional evidence build confidence and suggest a practice development approach.

The paper presents a workshop-based approach to improve confidence and standardize the use of functional evidence in variant classification through community discussion and consultation.

Scalable automated reanalysis of genomic data in research and clinical rare disease cohorts

The paper develops an automated tool for reanalyzing genomic data in rare disease cohorts, showing improved diagnostic yields through iterative reanalysis.

Dominant variants in major spliceosome U4 and U5 small nuclear RNA genes cause neurodevelopmental disorders through splicing disruption

The paper identifies de novo variants in RNU4-2 and RNU5B-1 as causes of neurodevelopmental disorders by disrupting splicing, with variant location and allele phase influencing clinical severity.

Consultation informs strategies to improve functional evidence use in variant classification

The paper surveys genetic professionals on functional evidence use in variant classification and identifies the need for expert recommendations and guidelines.

A humanized neuronal model system reveals key roles for manganese in neuronal endocytosis, calcium flux and mitochondrial bioenergetics

The paper establishes a humanized neuronal model to investigate the effects of manganese dysregulation on neuronal function and disease mechanisms.

Quantifying constraint in the human mitochondrial genome

The paper develops a mitochondrial constraint model applied to gnomAD data, revealing strong depletion of expected variation and identifying constrained regions in mtDNA.

The Australian Genomics Mitochondrial Flagship: A National Program Delivering Mitochondrial Diagnoses

The paper evaluates the diagnostic effectiveness of genomic sequencing in mitochondrial diseases using blood samples, finding a 55% diagnostic yield with higher rates in pediatric cases.

Valine restriction extends survival in a Drosophila model of short-chain enoyl-CoA hydratase 1 (ECHS1) deficiency

This study establishes a Drosophila model of ECHS1 deficiency and shows that valine restriction improves larval survival.

Untargeted proteomics enables ultra-rapid variant prioritization in mitochondrial and other rare diseases

This study uses untargeted proteomics to rapidly prioritize genetic variants in mitochondrial and other rare diseases, achieving functional evidence for 83% of cases in a cohort.

Gaps in the phenotype descriptions of ultra-rare genetic conditions: review and multi-center consensus reporting guidelines

The paper reviews phenotype reporting in genetic disorders and proposes guidelines to improve clinical relevance.

Unique Capabilities of Genome Sequencing for Rare Disease Diagnosis

This study evaluates genome sequencing's diagnostic yield in a cohort of undiagnosed rare disease patients, finding it solves 29.3% of cases with specific variant types not detectable by exome sequencing.

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network.

The paper identifies widespread transcription initiation at microsatellites across species and develops deep learning models to predict STR-associated transcription and its impact on disease variants.

Pathogenic variants in SMARCA5, a chromatin remodeler, cause a range of syndromic neurodevelopmental features

The paper identifies pathogenic variants in SMARCA5 as a cause of a neurodevelopmental syndrome with mild facial dysmorphia and developmental delay.

Genotype and defects in microtubule-based motility correlate with clinical severity in KIF1A Associated Neurological Disorder

This study links KIF1A variants to clinical severity in KAND by analyzing transport defects and protein dysfunction.

RNA sequencing identifies a cryptic exon caused by a deep intronic variant in NDUFB10 resulting in isolated Complex I deficiency.

The paper identifies a deep intronic variant in NDUFB10 causing a cryptic exon and isolated Complex I deficiency through RNA sequencing in two affected siblings.

Rapid diagnosis of SCA36 in a three-generation family using short-read whole genome sequencing data

This study uses whole genome sequencing to rapidly diagnose SCA36 in a family, demonstrating the feasibility and cost-effectiveness of WGS for repeat expansion detection.

Loss of function variants in PCYT1A causing spondylometaphyseal dysplasia with cone/rod dystrophy have broad consequences on lipid metabolism, chondrocyte differentiation, and lipid droplet formation.

This study investigates the effects of PCYT1A variants on lipid metabolism, chondrocyte differentiation, and lipid droplet formation using cellular models and lipidomics.