Deciphering the Pathogenetics of Rare Diseases by Multi-Omic Approaches: Disorders of Mitochondrial Energy Generation as an Exemplar

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

DH Hock, NJ Caruana, LN Semcesen, NJ Lake, LE Formosa, SSC Amarasekera, T Stait, S Tregoning, LE Frajman, AM Bournazos, DRL Robinson, M Ball, B Reljic, B Ryder, MJ Wallis, A Vasudevan, C Beck, H Peters, J Lee, NB Tan

2025-12-01

Background: Only half of individuals with suspected rare diseases receive a genetic diagnosis following genomic testing. A genetic..

The Australian Genomics Mitochondrial Flagship: A national program delivering mitochondrial diagnoses

R Rius, AG Compton, NL Baker, S Balasubramaniam, S Best, K Bhattacharya, K Boggs, T Boughtwood, J Braithwaite, D Bratkovic, A Bray, MJ Brion, J Burke, S Casauria, B Chong, D Coman, S Cowie, M Cowley, MG de Silva, MB Delatycki

2025-01-01

Purpose: Families living with mitochondrial diseases (MD) often endure prolonged diagnostic journeys and invasive testing, yet man..

TEFM variants impair mitochondrial transcription causing childhood-onset neurological disease

L Van Haute, E O’Connor, H Díaz-Maldonado, B Munro, K Polavarapu, DH Hock, G Arunachal, A Athanasiou-Fragkouli, M Bardhan, M Barth, D Bonneau, N Brunetti-Pierri, G Cappuccio, NJ Caruana, N Dominik, H Goel, G Helman, H Houlden, G Lenaers, K Mention

2023-12-01

Mutations in the mitochondrial or nuclear genomes are associated with a diverse group of human disorders characterized by impaired..

Multi-omics identifies large mitoribosomal subunit instability caused by pathogenic MRPL39 variants as a cause of pediatric onset mitochondrial disease

SSC Amarasekera, DH Hock, NJ Lake, SE Calvo, SW Grønborg, EI Krzesinski, DJ Amor, MC Fahey, C Simons, F Wibrand, VK Mootha, M Lek, S Lunke, Z Stark, E Østergaard, J Christodoulou, DR Thorburn, DA Stroud, AG Compton

2023-08-01

MRPL39 encodes one of 52 proteins comprising the large subunit of the mitochondrial ribosome (mitoribosome). In conjunction with 3..

Deficiency of the mitochondrial ribosomal subunit, MRPL50, causes autosomal recessive syndromic premature ovarian insufficiency

S Bakhshalizadeh, DH Hock, NA Siddall, BL Kline, R Sreenivasan, KM Bell, F Casagranda, S Kamalanathan, J Sahoo, N Narayanan, D Naik, V Suryadevara, AG Compton, SSC Amarasekera, R Kapoor, S Jaillard, A Simpson, G Robevska, J van den Bergen, S Pachernegg

2023-07-01

Premature ovarian insufficiency (POI) is a common cause of infertility in women, characterised by amenorrhea and elevated FSH unde..

Investigation of oxidative phosphorylation activity and complex composition in mitochondrial disease

K Thompson, DA Stroud, DR Thorburn, RW Taylor

2023-01-01

A multidisciplinary approach to the laboratory diagnosis of mitochondrial disease has long been applied, with crucial information ..

Distinct diagnostic trajectories in NBAS-associated acute liver failure highlights the need for timely functional studies

LS Akesson, R Rius, NJ Brown, J Rosenbaum, S Donoghue, M Stormon, C Chai, E Bordador, Y Guo, H Hakonarson, AG Compton, DR Thorburn, S Amarasekera, J Marum, A Monaco, C Lee, B Chong, S Lunke, Z Stark, J Christodoulou

2022-05-01

Variants of uncertain significance (VUS) are commonly found following genomic sequencing, particularly in ethnically diverse popul..

Modelling mitochondrial disease in human pluripotent stem cells: What have we learned?

CL McKnight, YC Low, DA Elliott, DR Thorburn, AE Frazier

2021-07-02

Mitochondrial diseases disrupt cellular energy production and are among the most complex group of inherited genetic disorders. Aff..

Application of genome sequencing from blood to diagnose mitochondrial diseases

R Rius, AG Compton, NL Baker, AE Welch, D Coman, MP Kava, AE Minoche, MJ Cowley, DR Thorburn, J Christodoulou

2021-04-01

Mitochondrial diseases can be caused by pathogenic variants in nuclear or mitochondrial DNA-encoded genes that often lead to multi..

Fatal Perinatal Mitochondrial Cardiac Failure Caused by Recurrent De Novo Duplications in the ATAD3 Locus

AE Frazier, AG Compton, Y Kishita, DH Hock, AME Welch, SSC Amarasekera, R Rius, LE Formosa, A Imai-Okazaki, D Francis, M Wang, NJ Lake, S Tregoning, JS Jabbari, A Lucattini, KR Nitta, A Ohtake, K Murayama, DJ Amor, G McGillivray

2021-01-15

Background: In about half of all patients with a suspected monogenic disease, genomic investigations fail to identify the diagnosi..

Multiomic analysis elucidates Complex I deficiency caused by a deep intronic variant in NDUFB10

G Helman, AG Compton, DH Hock, M Walkiewicz, GR Brett, L Pais, TY Tan, R De Paoli-Iseppi, MB Clark, J Christodoulou, SM White, DR Thorburn, DA Stroud, Z Stark, C Simons

2021-01-01

The diagnosis of Mendelian disorders following uninformative exome and genome sequencing remains a challenging and often unmet nee..

Recurrent de novo ATAD3 duplications cause fatal perinatal mitochondrial cardiomyopathy, persistent hyperlactacidemia, encephalopathy and heart-specific mitochondrial oxidative phosphorylation complex I deficiency.

AE Frazier, AG Compton, Y Kishita, DH Hock, AE Welch, SSC Amarasekera, R Rius, LE Formosa, A Imai-Okazaki, D Francis, M Wang, NJ Lake, S Tregoning, JS Jabbari, A Lucattini, R Nitta, A Ohtake, K Murayama, DJ Amor, G McGillivray

2020-12-01