Tony Roscioli
A5030784929- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- Craniofacial Disorders and Treatments
- Cleft Lip and Palate Research
- RNA modifications and cancer
- Connective tissue disorders research
- Prenatal Screening and Diagnostics
- Metabolism and Genetic Disorders
- BRCA gene mutations in cancer
- Mitochondrial Function and Pathology
- Neurogenetic and Muscular Disorders Research
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- Immunodeficiency and Autoimmune Disorders
- Genetic Syndromes and Imprinting
- Fibroblast Growth Factor Research
- Genetic factors in colorectal cancer
- Cancer-related gene regulation
- Neurological diseases and metabolism
- Lysosomal Storage Disorders Research
- Epigenetics and DNA Methylation
- RNA regulation and disease
- Erythrocyte Function and Pathophysiology
- Ubiquitin and proteasome pathways
Prince of Wales Hospital
2014-2025
Neuroscience Research Australia
2017-2025
Sydney Children's Hospital
2016-2025
UNSW Sydney
2015-2024
New South Wales Department of Health
2018-2024
University of Wisconsin–Madison
2024
Hanover College
2024
The University of Sydney
2007-2024
Genomics (United Kingdom)
2016-2024
Murdoch Children's Research Institute
2024
<h3>Background</h3> We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects <i>GRIN2B</i> encephalopathy explored potential prospects personalised medicine. <h3>Methods</h3> Data 48 individuals with de novo variants were collected from several diagnostic research cohorts, as well 43 patients the literature. Functional consequences response to memantine treatment investigated in vitro eventually translated into patient care. <h3>Results</h3> Overall, 86...
<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...
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...
Abstract Whole genome sequencing (WGS) improves Mendelian disorder diagnosis over whole exome (WES); however, additional diagnostic yields and costs remain undefined. We investigated differences between cost outcomes of WGS WES in a cohort with suspected disorders. was performed 38 WES-negative families derived from 64 family that previously underwent WES. For new diagnoses, contemporary reanalysis determined whether variants were diagnosable by original or unique to WGS. Diagnostic rates...
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...
Heterozygous mutations in p63 are associated with split hand/foot malformations (SHFM), orofacial clefting, and ectodermal abnormalities. Elucidation of the gene network that includes target genes regulatory elements may reveal new for other malformation disorders. We performed genome-wide DNA-binding profiling by chromatin immunoprecipitation (ChIP), followed deep sequencing (ChIP-seq) primary human keratinocytes, identified potential controlled p63. show binds to an enhancer element SHFM1...
Several known or putative glycosyltransferases are required for the synthesis of laminin-binding glycans on alpha-dystroglycan (αDG), including POMT1, POMT2, POMGnT1, LARGE, Fukutin, FKRP, ISPD and GTDC2. Mutations in these glycosyltransferase genes result defective αDG glycosylation reduced ligand binding by causing a clinically heterogeneous group congenital muscular dystrophies, commonly referred to as dystroglycanopathies. The most severe clinical form, Walker–Warburg syndrome (WWS), is...
Warburg Micro syndrome and Martsolf (MS) are heterogeneous autosomal-recessive developmental disorders characterized by brain, eye, endocrine abnormalities. Causative biallelic germline mutations have been identified in RAB3GAP1, RAB3GAP2, or RAB18, each of which encode proteins involved membrane trafficking. This report provides an up to date overview all known disease variants 29 previously published families 52 new families. One-hundred forty-four nine were investigated, identifying...
Certain mutations can cause proteins to accumulate in neurons, leading neurodegeneration. We recently showed, however, that upregulation of a wild-type protein, Ataxin1, caused by haploinsufficiency its repressor, the RNA-binding protein Pumilio1 (PUM1), also causes neurodegeneration mice. therefore searched for human patients with PUM1 mutations. identified eleven individuals either deletions or de novo missense variants who suffer developmental syndrome (Pumilio1-associated disability,...
Abstract Background Epileptic encephalopathies are a devastating group of neurological conditions in which etiological diagnosis can alter management and clinical outcome. Exome sequencing gene panel testing improve diagnostic yield but there is no cost‐effectiveness analysis their use or consensus on how to best integrate these tests into pathways. Methods We conducted retrospective study comparing trio exome with standard approach, for well‐phenotyped cohort 32 patients epileptic...
<h3>Objective</h3> To assess the benefits and limitations of whole genome sequencing (WGS) compared to exome (ES) or multigene panel (MGP) in molecular diagnosis developmental epileptic encephalopathies (DEE). <h3>Methods</h3> We performed WGS 30 comprehensively phenotyped DEE patient trios that were undiagnosed after first-tier testing, including chromosomal microarray either research ES (n = 15) diagnostic MGP 15). <h3>Results</h3> Eight diagnoses made 15 individuals who received prior...