A5028113025- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Congenital heart defects research
- Genomic variations and chromosomal abnormalities
- Connexins and lens biology
- BRCA gene mutations in cancer
- RNA modifications and cancer
- Diabetes Management and Research
- Health Systems, Economic Evaluations, Quality of Life
- RNA Research and Splicing
- Diabetes Treatment and Management
- Congenital Ear and Nasal Anomalies
- Pancreatic function and diabetes
- Neurogenetic and Muscular Disorders Research
- Retinal Development and Disorders
- Intraocular Surgery and Lenses
- Tracheal and airway disorders
- Ocular Disorders and Treatments
- Biochemical Analysis and Sensing Techniques
- VLSI and Analog Circuit Testing
- Primary Care and Health Outcomes
- Metabolism, Diabetes, and Cancer
- Genomics and Phylogenetic Studies
- Ion channel regulation and function
- Retinal Diseases and Treatments
Sydney Children’s Hospitals Network
2018-2025
Children's Hospital at Westmead
2016-2025
The University of Sydney
2016-2025
Children's Medical Research Institute
2015-2025
University of Wisconsin–Madison
2024
Hanover College
2024
World Institute on Disability
2023
Walter and Eliza Hall Institute of Medical Research
2020
Royal Children's Hospital
2020
Royal Brisbane and Women's Hospital
2020
<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...
Abstract Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily protein-coding genes 1 . Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify RNA RNU4-2 as a syndromic NDD gene. encodes U4 small nuclear (snRNA), which is critical component U4/U6.U5 tri-snRNP complex major spliceosome 2 We an 18 base pair region mapping two structural elements...
Genetic investigations of people with impaired development spoken language provide windows into key aspects human biology. Over 15 years after FOXP2 was identified, most speech and impairments remain unexplained at the molecular level. We sequenced whole genomes nineteen unrelated individuals diagnosed childhood apraxia speech, a rare disorder enriched for causative mutations large effect. Where DNA available from unaffected parents, we discovered de novo mutations, implicating genes,...
Congenital cataracts are a significant cause of lifelong visual loss. They may be isolated or associated with microcornea, microphthalmia, anterior segment dysgenesis (ASD) and glaucoma, there can syndromic associations. Genetic diagnosis is challenging due to marked genetic heterogeneity. In this study, next-generation sequencing (NGS) 32 cataract-associated genes was undertaken in 46 apparently nonsyndromic congenital cataract probands, around half sporadic familial cases. We identified...
<h3>Objective</h3> Determining the genetic basis of speech disorders provides insight into neurobiology human communication. Despite intensive investigation over past 2 decades, etiology most in children remains unexplained. To test hypothesis that have a etiology, we performed analysis with severe disorder, specifically childhood apraxia (CAS). <h3>Methods</h3> Precise phenotyping together research genome or exome were on referred primary diagnosis CAS. Gene coexpression and gene set...
Ligase IV syndrome is a rare differential diagnosis for Nijmegen breakage owing to shared predisposition lympho-reticular malignancies, significant microcephaly, and radiation hypersensitivity. Only 16 cases with mutations in LIG4 have been described date phenotypes varying from malignancy developmentally normal individuals, severe combined immunodeficiency early mortality. Here, we report the identification of biallelic truncating 11 patients microcephalic primordial dwarfism presenting...
Background Fetal akinesia and arthrogryposis are clinically genetically heterogeneous have traditionally been refractive to genetic diagnosis. The widespread availability of affordable genome-wide sequencing has facilitated accurate diagnosis gene discovery in these conditions. Methods We performed next generation (NGS) 190 probands with a multiplex congenita, distal arthrogryposis, fetal deformation sequence or multiple pterygium syndrome. This was combination bespoke neurogenetic disease...
Abstract Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily protein-coding genes 1 . Increasingly, large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify RNA RNU4-2 as a novel syndromic NDD gene. encodes U4 small nuclear (snRNA), which is critical component U4/U6.U5 tri-snRNP complex major spliceosome 2 We an 18 bp region mapping two...
Abstract The effects of metformin on glycaemia, insulin and c‐peptide levels, hepatic glucose production sensitivity (using the euglycaemic, hyperinsulinaemic clamp) were evaluated at fortnightly intervals in 9 Type 2 diabetic patients using a stepwise dosing protocol: Stage 1 ‐ no for four weeks; stage 500mg mane; 3 thrice daily; 4 – 1000mg daily. Results are expressed as Mean ± SEM. Fasting blood decreased from basal values (9.7 ±1.0 mmol/L) by 13% 2, 34% 41% (p<0.02 vs all stages;...
Significance Emotion-related responses, such as fear and anxiety, are important behavioral phenomena in most animal species, well humans. However, the underlying mechanisms of anxiety animals humans still largely unknown, disorders continue to represent a large unmet medical need human clinic. Animal models may speed up discovery these also lead betterment health. Herein, we report identification chemokine-like gene family, samdori ( sam ), present functional characterization sam2 . We...
Ocular anterior segment disorders (ASDs) are clinically and genetically heterogeneous, genetic diagnosis often remains elusive. In this study, we demonstrate the value of a combined analysis protocol using phenotypic, genomic, pedigree structure data to achieve conclusion.We utilized combination chromosome microarray, exome sequencing, genome sequencing with structural variant trio investigate cohort 41 predominantly sporadic cases.We identified likely causative variants in 54% (22/41)...
In Australia, little prevalence data around vision impairment exist. However, self-reported from the Australian Bureau of Statistics 2017–18 National Health Survey1 suggest that 800 000 people have a or are blind (excluding uncorrected refractive errors).2 The leading cause in working-age adults inherited retinal diseases (IRDs)3 — group genetic conditions primarily affect retina. Other than one particular gene therapy for biallelic RPE65-associated dystrophy, there no other clinically...
Implementation science based health care research is urgently needed for genomic and precision medicine in Australia Precision a tailored approach to health, incorporating an individual's genetic make-up, environment lifestyle, new frontier offering much promise disease prevention cure.1 Its recent rise has been largely driven by rapid advances medicine, with sequencing of code identifying opportunities care, therapies diagnostics. Genomics revolutionised many areas, including public (eg,...
Correct morphogenesis and differentiation are critical in development maintenance of the lens, which is a classic model system for epithelial disease. Through germline genomic analyses patients with lens eye abnormalities, we discovered functional mutations Signal Induced Proliferation Associated 1 Like 3 (SIPA1L3) gene, encodes previously uncharacterized member (SIPA1 or SPA1) family, role Rap1 signalling. Patient 1, de novo balanced translocation, 46,XY,t(2;19)(q37.3;q13.1), had ocular...
Abstract Cantú syndrome (CS), characterized by hypertrichosis, distinctive facial features, and complex cardiovascular abnormalities, is caused pathogenic variants in ABCC9 KCNJ8 genes. These genes encode gain‐of‐function mutations the regulatory (SUR2) pore‐forming (Kir6.1) subunits of K ATP channels, respectively, suggesting that channel‐blocking sulfonylureas could be a viable therapy. Here we report neonate with CS, carrying heterozygous variant (c.3347G>A, p.Arg1116His), born...
The RPGR gene encodes Retinitis Pigmentosa GTPase Regulator, a known interactor with ciliary proteins, which is involved in maintaining healthy photoreceptor cells. Variants are the main contributor to X-linked rod-cone dystrophy (RCD), and therapy approaches clinical trials. Hence, elucidation of pathogenicity novel variants important for patient opportunity. Here, we describe intronic variant, c.1415 − 9A>G, RCD, was classified as variant uncertain significance according current diagnostic...