Gianina Ravenscroft
A5076037048- Muscle Physiology and Disorders
- Cardiomyopathy and Myosin Studies
- Neurogenetic and Muscular Disorders Research
- Genetic Neurodegenerative Diseases
- Genomics and Rare Diseases
- RNA modifications and cancer
- Cellular transport and secretion
- Nuclear Structure and Function
- Genetics and Neurodevelopmental Disorders
- Hereditary Neurological Disorders
- Mitochondrial Function and Pathology
- Congenital heart defects research
- Ion channel regulation and function
- RNA Research and Splicing
- Cardiovascular Effects of Exercise
- Connective tissue disorders research
- Glycogen Storage Diseases and Myoclonus
- Neurological diseases and metabolism
- Ubiquitin and proteasome pathways
- Genetic Syndromes and Imprinting
- RNA and protein synthesis mechanisms
- Cellular Mechanics and Interactions
- RNA regulation and disease
- CRISPR and Genetic Engineering
- Tissue Engineering and Regenerative Medicine
The University of Western Australia
2016-2025
Harry Perkins Institute of Medical Research
2016-2025
Queen Elizabeth II Medical Centre
2014-2025
Royal Perth Hospital
2023-2024
Garvan Institute of Medical Research
2024
The University of Sydney
2024
ACT Government
2020-2024
Boston Children's Hospital
2023-2024
Uganda Wildlife Authority
2024
University of Helsinki
2023
Ataxia, causing imbalance, dizziness and falls, is a leading cause of neurological disability. We have recently identified biallelic intronic AAGGG repeat expansion in replication factor complex subunit 1 (RFC1) as the cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) major late onset ataxia. Here we describe full spectrum disease phenotype our first 100 genetically confirmed carriers expansions RFC1 identify sensory neuropathy common feature all cases to date. All...
The late-onset cerebellar ataxias (LOCAs) have largely resisted molecular diagnosis.We sequenced the genomes of six persons with autosomal dominant LOCA who were members three French Canadian families and identified a candidate pathogenic repeat expansion. We then tested for association between expansion disease in two independent case-control series - one (66 patients 209 controls) other German (228 199 controls). also genotyped 20 Australian 31 Indian index patients. assayed gene protein...
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...
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.
Nemaline myopathy (NM) is a genetic muscle disorder characterized by dysfunction and electron-dense protein accumulations (nemaline bodies) in myofibers. Pathogenic mutations have been described 9 genes to date, but the basis remains unknown many cases. Here, using an approach that combined whole-exome sequencing (WES) Sanger sequencing, we identified homozygous or compound heterozygous variants LMOD3 21 patients from 14 families with severe, usually lethal, NM. encodes leiomodin-3 (LMOD3),...
Objective Comprehensive clinical characterization of congenital titinopathy to facilitate diagnosis and management this important emerging disorder. Methods Using massively parallel sequencing we identified 30 patients from 27 families with 2 pathogenic nonsense, frameshift and/or splice site TTN mutations in trans . We then undertook a detailed analysis the clinical, histopathological imaging features these patients. Results All had prenatal or early onset hypotonia contractures. None...
Nemaline myopathy (NM) is a congenital that can result in lethal muscle dysfunction and thought to be disease of the sarcomere thin filament. Recently, several proteins unknown function have been implicated NM, but mechanistic basis their contribution remains unresolved. Here, we demonstrated loss muscle-specific protein, kelch-like family member 40 (KLHL40), results nemaline-like mice closely phenocopies abnormalities observed KLHL40-deficient patients. We determined KLHL40 localizes I band...
Fetal akinesia/hypokinesia, arthrogryposis and severe congenital myopathies are heterogeneous conditions usually presenting before or at birth. Although numerous causative genes have been identified for each of these disease groups, in many cases a specific genetic diagnosis remains elusive. Due to the emergence next generation sequencing, virtually entire coding region an individual’s DNA can now be analysed through “whole” exome enabling almost all known novel investigated disorders such...
See Cannon (doi: 10.1093/brain/awv400 ) for a scientific commentary on this article. Congenital myopathies are clinically and genetically heterogeneous group of muscle disorders characterized by congenital or early-onset hypotonia weakness, specific pathological features biopsy. The phenotype ranges from foetal akinesia resulting in utero neonatal mortality, to milder that not life-limiting. Over the past decade, more than 20 new myopathy genes have been identified. Most encode proteins...
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a progressive late-onset, neurological disease. Recently, pentanucleotide expansion in intron 2 of RFC1 was identified as the genetic cause CANVAS. We screened an Asian-Pacific cohort for CANVAS novel repeat motif, (ACAGG)exp, three affected individuals. This motif associated with additional clinical features including fasciculations elevated serum creatine kinase. These have not previously been described individuals...
A hallmark of neurodegeneration is defective protein quality control. The E3 ligase Listerin (LTN1/Ltn1) acts in a specialized control pathway-Ribosome-associated Quality Control (RQC)-by mediating proteolytic targeting incomplete polypeptides produced by ribosome stalling, and Ltn1 mutation leads to mice. Whether results from RQC whether contributes human disease have remained unknown. Here we show that three independently-generated mouse models with mutations different component the...
Expansions of short tandem repeats (STRs) cause many rare diseases. Expansion detection is challenging with short-read DNA sequencing data since supporting reads are often mapped incorrectly. Detection particularly difficult for "novel" STRs, which include new motifs at known loci or STRs absent from the reference genome. We developed STRling to efficiently count k-mers recover informative and call expansions novel STR loci. sensitive disease loci, has a low false discovery rate, resolves...
Abstract RFC1 disease, caused by biallelic repeat expansion in RFC1, is clinically heterogeneous terms of age onset, disease progression and phenotype. We investigated the role size influencing clinical variables disease. also assessed presence meiotic somatic instability repeat. In this study, we identified 553 patients carrying expansions measured 392 cases. Pearson’s coefficient was calculated to assess correlation between at onset. A Cox model with robust cluster standard errors adopted...
Abstract Oculopharyngodistal myopathy (OPDM) is an inherited manifesting with ptosis, dysphagia and distal weakness. Pathologically it characterised by rimmed vacuoles intranuclear inclusions on muscle biopsy. In recent years CGG • CCG repeat expansion in four different genes were identified OPDM individuals Asian populations. None of these have been found affected non-Asian ancestry. this study we describe the identification expansions ABCD3 , ranging from 118 to 694 repeats, 35 across...
Abstract The gold standard for facioscapulohumeral muscular dystrophy (FSHD) genetic diagnostic procedures was published in 2012. With the increasing complexity of genetics FSHD1 and 2, increase testing centers, start clinical trials FSHD, it is crucial to provide an update on our knowledge features FSHD loci renew international consensus molecular recommendations. To this end, members European Trial Network summarized evidence presented during 2022 ENMC meeting Genetic diagnosis, outcome...