John Christodoulou
A5045791231- Metabolism and Genetic Disorders
- Genetics and Neurodevelopmental Disorders
- Mitochondrial Function and Pathology
- Genomics and Rare Diseases
- RNA modifications and cancer
- Autism Spectrum Disorder Research
- Genomic variations and chromosomal abnormalities
- Biochemical and Molecular Research
- Family and Disability Support Research
- ATP Synthase and ATPases Research
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Folate and B Vitamins Research
- Chromatin Remodeling and Cancer
- Epigenetics and DNA Methylation
- Neonatal Health and Biochemistry
- RNA Research and Splicing
- Amino Acid Enzymes and Metabolism
- Trace Elements in Health
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- Immunodeficiency and Autoimmune Disorders
- Diet and metabolism studies
- SARS-CoV-2 and COVID-19 Research
- BRCA gene mutations in cancer
Royal Children's Hospital
2016-2025
Murdoch Children's Research Institute
2016-2025
The University of Melbourne
2016-2025
Victorian Clinical Genetics Services
2016-2025
The University of Sydney
2015-2024
Broad Institute
2024
Hospital for Sick Children
1992-2024
Boston Children's Hospital
2024
University College London
2023-2024
SickKids Foundation
1994-2024
Abstract Objective Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and often caused by mutations Methyl‐CpG‐binding protein 2 ( MECP2 ). Despite distinct clinical features, the accumulation of molecular information recent years has generated considerable confusion regarding diagnosis RTT. The purpose this work was to revise clarify 2002 consensus criteria for RTT anticipation treatment trials. Method RettSearch members,...
We investigated the etiology of Leigh syndrome in 67 Australian cases from 56 pedigrees, 35 with a firm diagnosis and 32 some atypical features. Biochemical or DNA defects were determined both groups, ie, 80% tightly defined group 41% "Leigh-like" group. Eleven patients had mitochondrial point mutations (nucleotide [nt] 8993 T to G, nt C, 8344 A G) 1 Leigh-like patient heteroplasmic deletion. Twenty-nine enzyme defects, 13 respiratory chain complex I, 9 IV, 7 pyruvate dehydrogenase (PDHC)....
Applying next-generation sequencing to 42 infants with mitochondrial disease highlights both the potential and challenge of using this technology in clinical diagnosis.
<h3>Importance</h3> Widespread adoption of rapid genomic testing in pediatric critical care requires robust clinical and laboratory pathways that provide equitable consistent service across health systems. <h3>Objective</h3> To prospectively evaluate the performance a multicenter network for ultra-rapid diagnosis public system. <h3>Design, Setting, Participants</h3> Descriptive feasibility study critically ill patients with suspected monogenic conditions treated at 12 Australian hospitals...
Children and families living with rare disease often experience significant health, psychosocial, economic burdens diagnostic delays. Experiences appear to be constant, regardless of the specific diagnosis. Systematically collected Australian data support policy response on diseases are scarce. We address this gap by providing survey results about 462 children aged <19 years approximately 200 different diseases.Of children, 96% were born in Australia, 55% male, median age was 8.9 (0-18.2)....
Overlapping clinical phenotypes and an expanding breadth complexity of genomic associations are a growing challenge in the diagnosis management Mendelian disorders. The functional consequences impacts variation may involve unique, disorder-specific, DNA methylation episignatures. In this study, we describe 19 novel episignature disorders compare findings alongside 38 previously established episignatures for total 57 associated with 65 genetic syndromes. We demonstrate increasing resolution...
Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk children, which is much lower than adults, remains unexplained. In an international cohort 112 children (&lt;16 yr old) hospitalized for pneumonia, we report 12 (10.7%) aged 1.5–13 with (7 children), severe (3), and moderate (2) 4 the 15 known clinically recessive biochemically complete IFN immunity: X-linked TLR7 deficiency children) autosomal...
Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies IFN-α2 alone (five patients) or with IFN-ω (eight from a cohort of 279 (4.7%) aged 6–73 yr influenza pneumonia. Nine four had antibodies high low concentrations, respectively, IFN-α2, six two IFN-ω. The patients’ increased A virus replication in both A549 cells reconstituted human airway epithelia. prevalence...
Critically ill infants and children with rare diseases need equitable access to rapid accurate diagnosis direct clinical management. Over 2 years, the Acute Care Genomics program provided whole-genome sequencing 290 families whose critically were admitted hospitals throughout Australia suspected genetic conditions. The average time result was 2.9 d diagnostic yield 47%. We performed additional bioinformatic analyses transcriptome in all patients who remained undiagnosed. Long-read functional...
Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize I interferons (IFNs)1,2, conferring a predisposition to life-threatening COVID-19 pneumonia3. Here we report patients NIK or RELB deficiency, specific of autosomal-dominant NF-κB2 also have neutralizing against IFNs and are at higher risk getting pneumonia. In these found only in individuals who heterozygous for variants associated both...
Genetic variants that cause rare disorders may remain elusive even after expansive testing, such as exome sequencing. The diagnostic yield of genome sequencing, particularly a negative evaluation, remains poorly defined.
Rett syndrome (RTT) is a debilitating neurological condition associated with mutations in the X-linked MECP2 gene, where apparently normal development seen prior to onset of cognitive and motor deterioration at 6-18 months life. A targeted deletion methyl-CpG-binding domain (MBD) coding region disruption mRNA splicing was introduced mouse, resulting complete loss Mecp2 transcripts protein. Postnatal comparison XO XY mutant allele-containing null mice revealed similar effects on mouse growth...
Abstract Rett syndrome, commonly associated with mutations of the methyl CpG‐binding protein 2 ( MECP2 ) gene, is characterised by an apparently normal early postnatal development followed deterioration acquired cognitive and motor coordination skills in childhood. To evaluate whether environmental factors may influence disease outcome we tested effect enrichment from 4 weeks age on behavioural competence mutant mice harboring a Mecp2 tm1Tam ‐null allele. Our findings show that improves...