David Ross Thorburn

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.

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.

Mitochondrial DNA variant detection in over 6,500 rare disease families by the systematic analysis of exome and genome sequencing data resolves undiagnosed cases

The paper identifies mitochondrial DNA variants in undiagnosed rare disease families using exome and genome sequencing data, leading to diagnoses in 0.4% of cases.

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.

alpha-Actinin-3 deficiency protects from the effects of acute cold exposure through altered skeletal muscle Ca2+ and OXPHOS signaling.

This study shows that alpha-actinin-3 deficiency improves cold tolerance through enhanced mitochondrial function and reduced muscle mass loss during acute cold exposure.

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.

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.

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.