Michel Tchan
A5004068647- Lysosomal Storage Disorders Research
- Metabolism and Genetic Disorders
- Genomics and Rare Diseases
- Glycogen Storage Diseases and Myoclonus
- Mitochondrial Function and Pathology
- Neurological disorders and treatments
- Diet and metabolism studies
- Genetic Neurodegenerative Diseases
- Renal and related cancers
- Genetics and Neurodevelopmental Disorders
- Trypanosoma species research and implications
- Cardiomyopathy and Myosin Studies
- Biochemical and Molecular Research
- Neonatal Health and Biochemistry
- Cellular transport and secretion
- Folate and B Vitamins Research
- Parkinson's Disease Mechanisms and Treatments
- Genetic and Kidney Cyst Diseases
- Neurological diseases and metabolism
- Neurogenetic and Muscular Disorders Research
- Genetic Syndromes and Imprinting
- Amino Acid Enzymes and Metabolism
- Cardiovascular Function and Risk Factors
- Sphingolipid Metabolism and Signaling
- RNA modifications and cancer
Westmead Hospital
2016-2025
The University of Sydney
2015-2025
James Cook University
2024
Melbourne Genomics Health Alliance
2024
Murdoch Children's Research Institute
2023-2024
John Wiley & Sons (United States)
2024
Ludwig-Maximilians-Universität München
2024
Friedrich Baur Stiftung
2024
Children's Hospital at Westmead
2008-2023
Children's Medical Research Institute
2023
More than 50 neurological and neuromuscular diseases are caused by short tandem repeat (STR) expansions, with 37 different genes implicated to date. We describe the use of programmable targeted long-read sequencing Oxford Nanopore’s ReadUntil function for parallel genotyping all known neuropathogenic STRs in a single assay. Our approach enables accurate, haplotype-resolved assembly DNA methylation profiling STR sites, from list predetermined candidates. This correctly diagnoses individuals...
Abstract Heterozygous mutations in KMT2B are associated with an early-onset, progressive and often complex dystonia (DYT28). Key characteristics of typical disease include focal motor features at presentation, evolving through a caudocranial pattern into generalized dystonia, prominent oromandibular, laryngeal cervical involvement. Although KMT2B-related is emerging as one the most common causes early-onset genetic much remains to be understood about full spectrum disease. We describe cohort...
PurposeThis trial aimed to assess the efficacy and safety of olipudase alfa enzyme replacement therapy for non–central nervous system manifestations acid sphingomyelinase deficiency (ASMD) in adults.MethodsA phase 2/3, 52 week, international, double-blind, placebo-controlled (ASCEND; NCT02004691/EudraCT 2015-000371-26) enrolled 36 adults with ASMD randomized 1:1 receive or placebo intravenously every 2 weeks intrapatient dose escalation 3 mg/kg. Primary endpoints were percent change from...
This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib).This is an international retrospective questionnaire study the use for management neutropenia/neutrophil dysfunction patients GSD Ib, conducted among respective health care providers from 24 countries across globe.Clinical data 112 were evaluated, representing a total 94 treatment years. The median age at start was 10.5 years...
ABSTRACT Objective The hereditary spastic‐ataxia spectrum disorders are a group of disabling neurological diseases. traditional genetic testing pathway is complex, multistep and leaves many cases unsolved. We aim to streamline improve this process using long‐read sequencing. Methods developed targeted sequencing strategy with the capacity characterise variation all types sizes within 469 disease‐associated genes, in single assay. applied cohort 34 individuals unsolved spastic‐ataxia. An...
Fabry disease (FD) is a rare and treatable X-linked lysosomal storage disorder. Cardiac involvement determines outcomes; therefore, detecting early changes important. Native T1 by cardiovascular magnetic resonance low, reflecting sphingolipid storage. Early phenotype development familiar in hypertrophic cardiomyopathy but unexplored FD. We explored the prehypertrophic cardiac of FD role storage.A prospective, international multicenter observational study 100 left ventricular...
Sphingolipid deposition in Fabry disease causes left ventricular (LV) hypertrophy, of which the accurate assessment is essential. Cardiovascular magnetic resonance (CMR) has been proposed as gold standard. However, there debate literature to whether papillary muscles and trabeculations (P&T) should be included LV mass (LVM). We examined accuracy 2 CMR methods assessing LVM volumes, including (M inc P&T) or excluding ex P&T, a cohort subjects (n = 20) compared matched control group 20)....
Background: Cardiovascular magnetic resonance can demonstrate myocardial processes in Fabry disease (FD), such as low native T1 (sphingolipid storage) and late gadolinium enhancement (LGE, scar). Recently, high T2 (edema) has been observed the basal inferolateral wall along with troponin elevation. We hypothesized that edema myocyte injury would be chronically associated have electrical, mechanical, associations FD. Methods: A prospective international multicenter study was conducted on 186...
Background: Cardiac response to enzyme replacement therapy (ERT) in Fabry disease is typically assessed by measuring left ventricular mass index using echocardiography or cardiovascular magnetic resonance, but neither quantifies myocardial biology. Low native T1 represents sphingolipid accumulation; late gadolinium enhancement with high T2 and troponin elevation reflects inflammation. We evaluated the effect of ERT on storage, inflammation, hypertrophy. Methods: Twenty patients starting (60%...
Introduction Detecting early cardiac involvement in Fabry disease (FD) is important because therapy may alter progression. Cardiovascular magnetic resonance (CMR) can detect T1 lowering, representing myocardial sphingolipid storage. In many diseases, mechanical dysfunction be detected by abnormal global longitudinal strain (GLS). We explored the relationship of and deposition FD. Methods An observational study 221 FD 77 healthy volunteers (HVs) who underwent CMR (LV volumes, mass, native T1,...
Abstract The phase III double-blind PROPEL study compared the novel two-component therapy cipaglucosidase alfa + miglustat (cipa mig) with alglucosidase placebo (alg pbo) in adults late-onset Pompe disease (LOPD). This ongoing open-label extension (OLE; NCT04138277) evaluates long-term safety and efficacy of cipa mig. Outcomes include 6-min walk distance (6MWD), forced vital capacity (FVC), creatine kinase (CK) hexose tetrasaccharide (Hex4) levels, patient-reported outcomes safety. Data are...
Diagnostic genomic sequencing is the emerging standard of care in nephrology. There a growing need to scale up implementation diagnostics nationally improve patient outcomes.
<h3>Objective</h3> Cardiac magnetic resonance (CMR) has the potential to provide early detection of cardiac involvement in Fabry disease. We aimed gain further insight into this by assessing a cohort patients using CMR. <h3>Methods/results</h3> Fifty genotype-positive subjects (age 45±2 years; 50% male) referred for CMR and 39 matched controls 40±2 59% were recruited. Patients had mean Mainz severity score index 15±2 (range 0–46), reflecting an overall mild degree disease severity. Compared...
There are few centres which specialise in the care of adults with inborn errors metabolism (IEM). To anticipate facilities and staffing needed at these centres, it is interest to know distribution different disorders.A survey was distributed through list-serve SSIEM Adult Metabolic Physicians group asking clinicians for number patients confirmed diagnoses, types diagnoses age diagnosis.Twenty-four adult responded our information on 6,692 patients. Of those patients, 510 were excluded not...
Dystonia is a clinically and genetically heterogeneous disorder genetic cause often difficult to elucidate. This the first study use whole genome sequencing (WGS) investigate dystonia in large sample of affected individuals.WGS was performed on 111 probands with heterogenous phenotypes. We analysis for coding non-coding variants, copy number variants (CNVs), structural (SVs). assessed an association between 10 known risk variants.A diagnosis obtained 11.7% (13/111) individuals. found that...