Mathew Wallis
A5090793628- Genomics and Rare Diseases
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- BRCA gene mutations in cancer
- DNA Repair Mechanisms
- Prenatal Screening and Diagnostics
- Tuberous Sclerosis Complex Research
- Metabolism and Genetic Disorders
- Cancer Genomics and Diagnostics
- Renal and related cancers
- Genetic factors in colorectal cancer
- RNA modifications and cancer
- Microtubule and mitosis dynamics
- Lung Cancer Research Studies
- Cancer therapeutics and mechanisms
- Cardiomyopathy and Myosin Studies
- Tumors and Oncological Cases
- Congenital heart defects research
- Polyomavirus and related diseases
- Language Development and Disorders
- Epigenetics and DNA Methylation
- Renal Diseases and Glomerulopathies
- Congenital Heart Disease Studies
Royal Hobart Hospital
2019-2025
University of Tasmania
2019-2025
Austin Health
2016-2024
Sydney Children's Hospital
2014-2024
Neuroscience Research Australia
2024
UNSW Sydney
2024
Murdoch Children's Research Institute
2024
Royal Children's Hospital
2024
Children's Hospital at Westmead
2024
Victorian Clinical Genetics Services
2024
COMMD1 deficiency results in defective copper homeostasis, but the mechanism for this has remained elusive. Here we report that is directly linked to early endosomes through its interaction with a protein complex containing CCDC22, CCDC93, and C16orf62. This COMMD/CCDC22/CCDC93 (CCC) interacts multisubunit WASH complex, an evolutionarily conserved system, which required endosomal deposition of F-actin cargo trafficking conjunction retromer. Interactions between subunit FAM21,...
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...
NF-κB is a master regulator of inflammation and has been implicated in the pathogenesis immune disorders cancer. Its regulation involves variety steps, including controlled degradation inhibitory IκB proteins. In addition, inactivation DNA-bound essential for its regulation. This step requires factor known as copper metabolism Murr1 domain–containing 1 (COMMD1), prototype member conserved gene family. While COMMD proteins have linked to ubiquitination pathway, little else about other family...
Abstract Mendelian-like inheritance of germline DNA methylation in cancer susceptibility genes has been previously reported. We aimed to scan the genome for heritable marks associated with breast by studying 25 Australian multiple-case families. Here we report genome-wide measured 210 peripheral blood samples provided family members using Infinium HumanMethylation450. develop and apply a new statistical method identify based on complex segregation analysis. estimate carrier probabilities...
To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease.We performed clinically accredited singleton ES a prospectively ascertained cohort 204 assessed multidisciplinary renal genetics clinics at four tertiary hospitals Melbourne, Australia.ES identified molecular diagnosis 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age presentation was independently associated an (p < 0.001). Of those...
BackgroundGenomic sequencing technology allows for identification of reproductive couples with an increased chance, as compared that in the general population, having a child autosomal recessive or X-linked genetic condition.MethodsWe investigated feasibility, acceptability, and outcomes nationwide, couple-based carrier screening program Australia part Mackenzie's Mission project. Health care providers offered to persons before pregnancy early pregnancy. The results obtained from testing at...
Topoisomerase III beta (TOP3B) is one of the least understood members topoisomerase family proteins and remains enigmatic. Our recent data shed light on function relevance TOP3B to disease. A homozygous deletion for gene was identified in a patient with bilateral renal cancer. Analyses both modelled human cells show disruption causes genome instability rise DNA damage chromosome bridging (mis-segregation). The primary molecular defect underlying this pathology significant increase R-loop...
Reproductive genetic carrier screening (RGCS) provides people with information about their chance of having children autosomal recessive or X-linked conditions, enabling informed reproductive decision-making. RGCS is recommended to be offered all couples during preconception in early pregnancy. However, cost and a lack awareness may prevent access. To address this, the Australian Government funded Mackenzie’s Mission—the Genetic Carrier Screening Project. Mission aims assess acceptability...
PURPOSE Establishing accurate age-related penetrance figures for the broad range of cancer types that occur in individuals harboring a pathogenic germline variant TP53 gene is essential to determine most effective clinical management strategies. These also permit optimal use cosegregation data classification variants unknown significance. Penetrance estimation can easily be affected by bias from ascertainment criteria, an issue not commonly addressed previous studies. MATERIALS AND METHODS...
Childhood apraxia of speech (CAS), the prototypic severe childhood disorder, is characterized by motor programming and planning deficits. Genetic factors make substantive contributions to CAS aetiology, with a monogenic pathogenic variant identified in third cases, implicating around 20 single genes date. Here we aimed identify molecular causation 70 unrelated probands ascertained CAS. We performed trio genome sequencing. Our bioinformatic analysis examined nucleotide, indel, copy number,...
Abstract Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants the two genes that encode histone H3.3 ( H3-3A / H3F3A and H3-3B H3F3B ) [1–4]. This characterized developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, abnormal neuroimaging [1, 5]. BLBS was initially categorized as a progressive neurodegenerative de novo heterozygous either or Here, we analyze data of 58 previously published...
The cerebellar ataxias (CAs) are a heterogeneous group of disorders characterized by progressive incoordination. Seventeen repeat expansion (RE) loci have been identified as the primary genetic cause and account for >80% diagnoses. Despite this, diagnostic testing is limited inefficient, often utilizing single gene assays. This study evaluates effectiveness long- short-read sequencing tools CA. We recruited 110 individuals (48 females, 62 males) with clinical diagnosis Short-read genome...
Abstract The underpinnings of mild to moderate neurodevelopmental delay remain elusive, often leading late diagnosis and interventions. Here, we present data on exome genome sequencing as well array analysis 13 individuals that point pathogenic, heterozygous, mostly de novo variants in WDFY3 (significant enrichment P = 0.003) a monogenic cause non-specific delay. Nine were protein-truncating four missense. Overlapping symptoms included delay, intellectual disability, macrocephaly,...
Background Dilated cardiomyopathy may be heritable but shows extensive genetic heterogeneity. The utility of whole exome sequencing as a first‐line test for patients with dilated in contemporary “real‐world” setting has not been specifically established. Using rigorous, evidence‐based variant interpretation, we aimed to identify the prevalence molecular diagnosis clinical setting. Methods and Results Whole was performed eligible (n=83) idiopathic or familial cardiomyopathy. Variants were...
Objective Dominant spinocerebellar ataxias (SCA) are characterized by genetic heterogeneity. Some mapped and named loci remain without a causal gene identified. Here we applied next generation sequencing (NGS) to uncover the etiology of SCA25 locus . Methods Whole‐exome whole‐genome were performed in families linked , including French family which was originally mapped. Whole exome sequence data interrogated cohort 796 ataxia patients unknown etiology. Results The phenotype spans slowly...
Australia will take a world-first step towards offering preventive DNA screening through the public health care system In adult-onset genomic conditions, such as hereditary breast and ovarian cancer (HBOC), Lynch syndrome familial hypercholesterolaemia, certain variants confer high risk of developing future disease.1 for these conditions could thereby identify medically actionable genetic factors, prompting timely management informed decision making from early adulthood to facilitate...
Tuberous sclerosis complex (TSC) is a multi-system genetic disorder. Most patients have germline mutations in TSC1 or TSC2 but, 10%–15% do not TSC1/TSC2 detected on routine clinical testing. We investigated the contribution of low-level mosaic unsolved sporadic and families with TSC. Thirty-one TSC negative testing eight suspected parental mosaicism were sequenced using deep panel sequencing followed by droplet digital polymerase chain reaction. Pathogenic variants found 22/31 (71%)...