2024
The Australian Genomics Mitochondrial Flagship: A National Program Delivering Mitochondrial Diagnoses.
Rius R, Compton A, Baker N, Balasubramaniam S, Best S, Bhattacharya K, Boggs K, Boughtwood T, Braithwaite J, Bratkovic D, Bray A, Brion M, Burke J, Casauria S, Chong B, Coman D, Cowie S, Cowley M, de Silva M, Delatycki M, Edwards S, Ellaway C, Fahey M, Finlay K, Fletcher J, Frajman L, Frazier A, Gayevskiy V, Ghaoui R, Goel H, Goranitis I, Haas M, Hock D, Howting D, Jackson M, Kava M, Kemp M, King-Smith S, Lake N, Lamont P, Lee J, Long J, MacShane M, Madelli E, Martin E, Marum J, Mattiske T, McGill J, Metke A, Murray S, Panetta J, Phillips L, Quinn M, Ryan M, Schenscher S, Simons C, Smith N, Stroud D, Tchan M, Tom M, Wallis M, Ware T, Welch A, Wools C, Wu Y, Christodoulou J, Thorburn D. The Australian Genomics Mitochondrial Flagship: A National Program Delivering Mitochondrial Diagnoses. Genetics In Medicine 2024, 101271. PMID: 39305161, DOI: 10.1016/j.gim.2024.101271.Peer-Reviewed Original ResearchGenome sequencePhenocopy genesMitochondrial diseaseMtDNA sequencesMtDNA deletionsMD geneMtDNAChildhood-onset diseaseDiagnostic journeyDiagnostic yieldMolecular diagnosisGenesNational studySequenceGene etiologySuspected MDDiagnostic pathwayIncrease diagnostic yieldPediatric-onsetOnset diseaseAdult onsetAdult patientsChildrenSkeletal muscleScores
2023
Multi-omics identifies large mitoribosomal subunit instability caused by pathogenic MRPL39 variants as a cause of pediatric onset mitochondrial disease
Amarasekera S, Hock D, Lake N, Calvo S, Grønborg S, Krzesinski E, Amor D, Fahey M, Simons C, Wibrand F, Mootha V, Lek M, Lunke S, Stark Z, Østergaard E, Christodoulou J, Thorburn D, Stroud D, Compton A. Multi-omics identifies large mitoribosomal subunit instability caused by pathogenic MRPL39 variants as a cause of pediatric onset mitochondrial disease. Human Molecular Genetics 2023, 32: 2441-2454. PMID: 37133451, PMCID: PMC10360397, DOI: 10.1093/hmg/ddad069.Peer-Reviewed Original ResearchConceptsQuantitative proteomicsMitochondrial oxidative phosphorylation systemProtein complex assemblySmall mitoribosomal subunitExome sequencingOxidative phosphorylation systemMitochondrial deoxyribonucleic acidMitochondrial ribosomesMitoribosomal subunitDeoxyribonucleic acidGene-disease associationsLarge subunitOXPHOS disordersSmall subunitComplex assemblyPhosphorylation systemProteomic dataComplex abundanceFunctional validationDisease genesGenome sequencingMitochondrial diseaseCryptic exonGene matchingProtein signatures
2020
Fatal Perinatal Mitochondrial Cardiac Failure Caused by Recurrent De Novo Duplications in the ATAD3 Locus
Frazier A, Compton A, Kishita Y, Hock D, Welch A, Amarasekera S, Rius R, Formosa L, Imai-Okazaki A, Francis D, Wang M, Lake N, Tregoning S, Jabbari J, Lucattini A, Nitta K, Ohtake A, Murayama K, Amor D, McGillivray G, Wong F, van der Knaap M, Vermeulen R, Wiltshire E, Fletcher J, Lewis B, Baynam G, Ellaway C, Balasubramaniam S, Bhattacharya K, Freckmann M, Arbuckle S, Rodriguez M, Taft R, Sadedin S, Cowley M, Minoche A, Calvo S, Mootha V, Ryan M, Okazaki Y, Stroud D, Simons C, Christodoulou J, Thorburn D. Fatal Perinatal Mitochondrial Cardiac Failure Caused by Recurrent De Novo Duplications in the ATAD3 Locus. Med 2020, 2: 49-73.e10. PMID: 33575671, PMCID: PMC7875323, DOI: 10.1016/j.medj.2020.06.004.Peer-Reviewed Original ResearchConceptsMitochondrial diseasePediatric mitochondrial diseaseMitochondrial oxidative phosphorylation complexes IOxidative phosphorylation complexes IDominant-negative mannerStudy of RNADNA sequencing techniquesSegmental duplicationsGenomic strategiesQuantitative proteomicsWhole genomeGenomic investigationsGene locusRepetitive regionsSequencing techniquesGenomeComplex IRecessive deletionsLociWhole exomeDuplicationMonogenic diseasesDe novo duplicationExome sequencingPontocerebellar hypoplasia
2019
A patient with homozygous nonsense variants in two Leigh syndrome disease genes: Distinguishing a dual diagnosis from a hypomorphic protein‐truncating variant
Lake N, Formosa L, Stroud D, Ryan M, Calvo S, Mootha V, Morar B, Procopis P, Christodoulou J, Compton A, Thorburn D. A patient with homozygous nonsense variants in two Leigh syndrome disease genes: Distinguishing a dual diagnosis from a hypomorphic protein‐truncating variant. Human Mutation 2019, 40: 893-898. PMID: 30981218, PMCID: PMC6661004, DOI: 10.1002/humu.23753.Peer-Reviewed Original ResearchConceptsProtein-truncating variantsCI assemblyC-terminusLeigh syndromeMutant proteinsKnockout cellsDisease genesUncharacterized variantsHypomorphic effectPathogenic variantsLeigh-like syndromeMitochondrial diseaseWhole-exome sequencingGenomic criteriaFunctional studiesAmino acidsGenesTIMMDC1Homozygous nonsense variantPatient's clinical phenotypeClinical phenotypeExome sequencingNonsense variantMedical GeneticsDual diagnosis
2015
Leigh syndrome: One disorder, more than 75 monogenic causes
Lake N, Compton A, Rahman S, Thorburn D. Leigh syndrome: One disorder, more than 75 monogenic causes. Annals Of Neurology 2015, 79: 190-203. PMID: 26506407, DOI: 10.1002/ana.24551.Peer-Reviewed Original Research