ORCID Profile
0000-0002-5828-315X
Current Organisations
Queensland University of Technology
,
The Mendel Institute
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Publisher: Wiley
Date: 27-06-2016
DOI: 10.1002/AJMG.A.37803
Abstract: Hennekam lymphangiectasia-lymphedema syndrome is an autosomal recessive disorder, with 25% of patients having mutations in CCBE1. We identified a family with two brothers presenting with primary lymphedema, and performed exome sequencing to determine the cause of their disease. Analysis of four family members showed that both affected brothers had the same rare compound heterozygous mutations in CCBE1. The presumed paternally inherited NM_133459.3:c.310G>A p.(Asp104Asn), lies adjacent to other known pathogenic CCBE1 mutations, while the maternally inherited NM_133459.3:c.80T>C p.(Leu27Pro) lies in the CCBE1 signal peptide, which has not previously been associated with disease. Functional analysis in a zebrafish model of lymphatic disease showed that both mutations lead to CCBE1 loss of function, confirming the pathogenicity of these variants and expanding the genotypic spectrum of lymphatic disorders. © 2016 Wiley Periodicals, Inc.
Publisher: Wiley
Date: 09-10-2006
DOI: 10.1111/J.1399-0004.2006.00700.X
Abstract: Mulibrey nanism is a rare autosomal recessive growth disorder with prenatal onset, including occasional progressive cardiopathy, characteristic facial features, failure of sexual maturation, insulin resistance with type 2 diabetes, and an increased risk for Wilms' tumor. Mulibrey nanism is prevalent in the Finnish population and appears extremely rare elsewhere. However, cases outside of Finland may be underdiagnosed or misdiagnosed as having the 3-M or Silver-Russell syndrome, two important differential diagnostic disorders. Here, we report the first Australian patient with mulibrey nanism, in whom the occurrence of Wilms' tumor suggested the correct diagnosis. This was confirmed by the identification of two novel mutations in tripartite motif protein 37 (TRIM37) encoding a RING finger ubiquitin E3 ligase. Both mutations, the p.Cys109Ser B-box missense mutation and the p.Glu271_Ser287del in-frame deletion in the tumor necrosis factor receptor associated factor (TRAF) domain alter the subcellular localization of TRIM37. As both the B-box and the TRAF domains are predicted to be important for mediating the protein-protein interactions, these mutations may help the understanding of the cellular interactions of TRIM37. Our findings imply the importance of early molecular diagnostics in cases of suspected mulibrey nanism and of identifying novel mutations with potential relevance for unraveling the underlying molecular pathology. Ultrasound surveillance for Wilms' tumor is recommended for children with mulibrey nanism.
Publisher: Springer Science and Business Media LLC
Date: 05-10-2022
DOI: 10.1038/S41586-022-05259-Y
Abstract: Loss of Paneth cells and their antimicrobial granules compromises the intestinal epithelial barrier and is associated with Crohn's disease, a major type of inflammatory bowel disease
Publisher: American Society of Hematology
Date: 25-06-2020
Abstract: A goal in precision medicine is to use patient-derived material to predict disease course and intervention outcomes. Here, we use mechanistic observations in a preclinical animal model to design an ex vivo platform that recreates genetic susceptibility to T-cell–mediated damage. Intestinal graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation. We found that intestinal GVHD in mice deficient in Atg16L1, an autophagy gene that is polymorphic in humans, is reversed by inhibiting necroptosis. We further show that cocultured allogeneic T cells kill Atg16L1-mutant intestinal organoids from mice, which was associated with an aberrant epithelial interferon signature. Using this information, we demonstrate that pharmacologically inhibiting necroptosis or interferon signaling protects human organoids derived from in iduals harboring a common ATG16L1 variant from allogeneic T-cell attack. Our study provides a roadmap for applying findings in animal models to in idualized therapy that targets affected tissues.
Publisher: Massachusetts Medical Society
Date: 28-02-2019
Publisher: Springer Science and Business Media LLC
Date: 10-06-2019
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1038/GIM.2017.214
Abstract: The craniosynostoses are characterized by premature fusion of one or more cranial sutures. The relative contribution of previously reported genes to craniosynostosis in large cohorts is unclear. Here we report on the use of a massively parallel sequencing panel in in iduals with craniosynostosis without a prior molecular diagnosis. A 20-gene panel was designed based on the genes' association with craniosynostosis, and clinically validated through retrospective testing of an Australian and New Zealand cohort of 233 in iduals with craniosynostosis in whom previous testing had not identified a causative variant within FGFR1-3 hot-spot regions or the TWIST1 gene. An additional 76 in iduals were tested prospectively. Pathogenic or likely pathogenic variants in non-FGFR genes were identified in 43 in iduals, with diagnostic yields of 14% and 15% in retrospective and prospective cohorts, respectively. Variants were identified most frequently in TCF12 (N = 22) and EFNB1 (N = 8), typically in in iduals with nonsyndromic coronal craniosynostosis or TWIST1-negative clinically suspected Saethre-Chotzen syndrome. Clinically significant variants were also identified in ALX4, EFNA4, ERF, and FGF10. These findings support the clinical utility of a massively parallel sequencing panel for craniosynostosis. TCF12 and EFNB1 should be included in genetic testing for nonsyndromic coronal craniosynostosis or clinically suspected Saethre-Chotzen syndrome.
Publisher: Wiley
Date: 09-11-2006
DOI: 10.1111/J.1440-1754.2006.00983.X
Abstract: Neonatal severe hyperparathyroidism is a rare condition that presents as striking hyperparathyroidism, hypercalcaemia, and metabolic bone disease. The aetiology needs to be determined soon after diagnosis to direct appropriate management and to determine an accurate prognosis. Taking a family history is a valuable clinical tool in paediatric medicine. Presented here is the case of a neonate presenting with severe hyperparathyroidism. Obtaining the family history, coupled with basic parental studies, enabled a rapid aetiological diagnosis, which allowed for conservative management.
Publisher: Wiley
Date: 26-03-2010
DOI: 10.1002/BDRA.20663
Abstract: The causes of septo-optic dysplasia, amyoplasia, and gastroschisis are mostly unknown. We present a patient with septo-optic dysplasia and amyoplasia. We also present a patient with features of septo-optic dysplasia, gray matter heterotopias, and gastroschisis. These previously unreported combinations provide further support for vascular disruption in embryonic or fetal life as an etiological factor in these conditions.
Publisher: Springer Science and Business Media LLC
Date: 18-02-2015
Publisher: Springer Science and Business Media LLC
Date: 24-11-2015
DOI: 10.1038/NG.3153
Abstract: Temple-Baraitser syndrome (TBS) is a multisystem developmental disorder characterized by intellectual disability, epilepsy, and hypoplasia or aplasia of the nails of the thumb and great toe. Here we report damaging de novo mutations in KCNH1 (encoding a protein called ether à go-go, EAG1 or KV10.1), a voltage-gated potassium channel that is predominantly expressed in the central nervous system (CNS), in six in iduals with TBS. Characterization of the mutant channels in both Xenopus laevis oocytes and human HEK293T cells showed a decreased threshold of activation and delayed deactivation, demonstrating that TBS-associated KCNH1 mutations lead to deleterious gain of function. Consistent with this result, we find that two mothers of children with TBS, who have epilepsy but are otherwise healthy, are low-level (10% and 27%) mosaic carriers of pathogenic KCNH1 mutations. Consistent with recent reports, this finding demonstrates that the etiology of many unresolved CNS disorders, including epilepsies, might be explained by pathogenic mosaic mutations.
Publisher: Wiley
Date: 11-10-2013
DOI: 10.1002/AJMG.C.31378
Abstract: Craniosynostosis is one of the most common craniofacial disorders encountered in clinical genetics practice, with an overall incidence of 1 in 2,500. Between 30% and 70% of syndromic craniosynostoses are caused by mutations in hotspots in the fibroblast growth factor receptor (FGFR) genes or in the TWIST1 gene with the difference in detection rates likely to be related to different study populations within craniofacial centers. Here we present results from molecular testing of an Australia and New Zealand cohort of 630 in iduals with a diagnosis of craniosynostosis. Data were obtained by Sanger sequencing of FGFR1, FGFR2, and FGFR3 hotspot exons and the TWIST1 gene, as well as copy number detection of TWIST1. Of the 630 probands, there were 231 who had one of 80 distinct mutations (36%). Among the 80 mutations, 17 novel sequence variants were detected in three of the four genes screened. In addition to the proband cohort there were 96 in iduals who underwent predictive or prenatal testing as part of family studies. Dysmorphic features consistent with the known FGFR1-3/TWIST1-associated syndromes were predictive for mutation detection. We also show a statistically significant association between splice site mutations in FGFR2 and a clinical diagnosis of Pfeiffer syndrome, more severe clinical phenotypes associated with FGFR2 exon 10 versus exon 8 mutations, and more frequent surgical procedures in the presence of a pathogenic mutation. Targeting gene hot spot areas for mutation analysis is a useful strategy to maximize the success of molecular diagnosis for in iduals with craniosynostosis.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2008
Publisher: Cambridge University Press (CUP)
Date: 13-03-2015
DOI: 10.1017/THG.2015.4
Abstract: Dr John MacMillan, Senior Staff Specialist at Genetic Health Queensland and Associate Professor of Medicine at The University of Queensland, passed away on December 21, 2014, aged 55 years. John was founding director at Genetic Health Queensland and was well known for his research contribution into the genetic basis of neurological disease.
Publisher: Oxford University Press (OUP)
Date: 22-12-2015
DOI: 10.1093/BRAIN/AWV352
Publisher: Wiley
Date: 17-01-2008
DOI: 10.1002/AJMG.A.32129
Abstract: We present a case of a male with severe mental retardation, seizure disorder, and absence/hypoplasia of the thumb and great toe nails. This combination of clinical findings has been reported only once previously. We suggest it represents a distinct syndrome. Our case has the additional finding of broad thumbs.
Publisher: Wiley
Date: 08-2016
DOI: 10.1111/IMJ.13156
Abstract: The Queensland branch of the Royal Australasian College of Physicians (RACP) commissioned this study to update their workforce profile and examine rural practice. The present investigation aimed to describe characteristics of Queensland physicians and determine the influence of childhood and training locations on current rural practice. A cross-sectional online survey, conducted 4 July-4 November 2013, was administered to Fellows of The RACP, Queensland. Descriptive statistics report characteristics and logistic regression analyses identify associations and interactions. The outcome measure was current practice location using the Australian Standard Geographic Classification - Remoteness Area. Data were obtained for 633 physicians. Their average age was 49.5 years, a third was female and a quarter was in rural practice. Rural practice was associated with a rural childhood (odds ratio (OR) (95% confidence interval, CI) 1.89 (1.10, 3.27) P = 0.02) and any time spent as an intern (OR 4.07 (2.12, 7.82) P < 0.001) or registrar (OR 4.00 (2.21, 7.26) P < 0.001) in a rural location. Physicians with a rural childhood and rural training were most likely to be in rural practice. However, those who had a metropolitan childhood and a rural internship were approximately five times more likely to be working in rural practice than physicians with no rural exposure (OR 5.33 (1.61, 17.60) P < 0.01). The findings demonstrate the positive effect of rural vocational training on rural practice. A prospective study would determine if recent changes to the Basic Physician Training Pathway and the Basic Paediatric Training Network (more rural training than previous pathways) increases the rate of rural practice.
Publisher: Wiley
Date: 16-07-2009
DOI: 10.1002/AJMG.A.32985
Publisher: Cambridge University Press (CUP)
Date: 28-11-2014
DOI: 10.1017/THG.2014.65
Abstract: Since the discovery in 1989 that mutations in cystic fibrosis transmembrane conductance regulator ( CFTR ) underlie cystic fibrosis (CF), the most common life shortening genetic disorder in Caucasians, it has been possible to identify heterozygous mutation carriers at risk of having affected children. The Human Genetics Society of Australasia has produced a position statement with recommendations in relation to population-based screening for CF. These include: (1) that screening should be offered to all relatives of people with or carriers of CF (cascade testing) as well as to all couples planning to have children or who are pregnant (2) the minimum CFTR mutation panel to be tested consists of 17 mutations which are those mutations that are associated with typical CF and occur with a frequency of 0.1% or higher among in iduals diagnosed with CF in Australasia (3) that genetic counselling is offered to all couples where both members are known to have one or two CFTR mutations and that such couples are given the opportunity to meet with a physician with expertise in the management of CF as well as a family/in idual affected by the condition.
Publisher: Wiley
Date: 16-10-2020
DOI: 10.1002/AJMG.A.61920
Publisher: Wiley
Date: 03-08-2010
DOI: 10.1002/AJMG.A.33574
Abstract: Temple-Baraitser syndrome, previously described in two unrelated patients, is the association of severe mental retardation and abnormal thumbs and great toes. We report two additional unrelated patients with Temple-Baraitser syndrome, review clinical and radiological features of previously reported cases and discuss mode of inheritance. Patients share a consistent pattern of anomalies: hypo or aplasia of the thumb and great toe nails and broadening and/or elongation of the thumbs and halluces, which have a tubular aspect. All patients were born to unrelated parents and occurred as a single occurrence in multiple sibships, suggesting sporadic inheritance from a de novo mutation mechanism. Comparative genomic hybridization in Patients 1, 2 and 3 did not reveal any copy number variations. We confirm that Temple-Baraitser syndrome represents a distinct syndrome, probably unrecognized, possibly caused by a de novo mutation in a not yet identified gene.
Publisher: Wiley
Date: 13-02-2008
DOI: 10.1111/J.1399-0004.2007.00960.X
Abstract: We report on a 4-year-old male with an interstitial tandem duplication of Xq21.1-q21.31 who presented with clinical features of Prader-Willi syndrome (PWS). The duplication was maternally inherited. Abnormalities of the X chromosome have previously been reported in association with a PWS phenotype, but to date, specific duplications of Xq21.1-q21.31 have not. We refined the chromosomal breakpoints seen on initial G-banded karyotyping in our case with comparative genomic hybridization by microarray (array CGH). The duplication was between 11.1 and 14.4 Mb in length and overlaps with three loci to which mental retardation with PWS-like features have been previously mapped, showing the utility of array CGH in helping to identify candidate genes. We conclude that duplication of chromosomal region Xq21.1-q21.31 potentially results in a PWS-like phenotype. Reviewing the literature on similar duplications, we further conclude that distal Xq duplications can result in features typically seen in infants with PWS, while proximal duplications can result in features typically seen in older children and adults with PWS. Duplications of chromosome Xq should be considered in the differential diagnosis of PWS, especially in males.
Publisher: Hindawi Limited
Date: 08-02-2011
DOI: 10.1002/HUMU.21457
Publisher: Elsevier BV
Date: 08-2021
Publisher: Wiley
Date: 24-03-2017
Publisher: Hindawi Limited
Date: 29-07-2010
DOI: 10.1002/HUMU.21328
Publisher: Hindawi Limited
Date: 21-06-2011
DOI: 10.1002/HUMU.21505
Abstract: Mutations in the PORCN gene were first identified in Goltz-Gorlin syndrome patients in 2007. Since then, several reports have been published describing a large variety of genetic defects resulting in the Goltz-Gorlin syndrome, and mutations or deletions were also reported in angioma serpiginosum, the pentalogy of Cantrell and Limb-Body Wall Complex. Here we present a review of the published mutations in the PORCN gene to date and report on seven new mutations together with the corresponding clinical data. Based on the review we have created a Web-based locus-specific database that lists all identified variants and allows the inclusion of future reports. The database is based on the Leiden Open (source) Variation Database (LOVD) software, and is accessible online at www.lovd.nl orcn. At present, the database contains 106 variants, representing 68 different mutations, scattered along the whole coding sequence of the PORCN gene, and 12 large gene rearrangements, which brings up to 80 the number of unique mutations identified in Goltz-Gorlin syndrome patients.
Publisher: Association for the Advancement of Artificial Intelligence (AAAI)
Date: 03-04-2020
Abstract: Meta-learning for few-shot learning allows a machine to leverage previously acquired knowledge as a prior, thus improving the performance on novel tasks with only small amounts of data. However, most mainstream models suffer from catastrophic forgetting and insufficient robustness issues, thereby failing to fully retain or exploit long-term knowledge while being prone to cause severe error accumulation. In this paper, we propose a novel Continual Meta-Learning approach with Bayesian Graph Neural Networks (CML-BGNN) that mathematically formulates meta-learning as continual learning of a sequence of tasks. With each task forming as a graph, the intra- and inter-task correlations can be well preserved via message-passing and history transition. To remedy topological uncertainty from graph initialization, we utilize Bayes by Backprop strategy that approximates the posterior distribution of task-specific parameters with amortized inference networks, which are seamlessly integrated into the end-to-end edge learning. Extensive experiments conducted on the miniImageNet and tieredImageNet datasets demonstrate the effectiveness and efficiency of the proposed method, improving the performance by 42.8% compared with state-of-the-art on the miniImageNet 5-way 1-shot classification task.
Publisher: Wiley
Date: 24-01-2020
DOI: 10.1002/AJMG.A.61494
Abstract: Jansen metaphyseal chondrodysplasia (JMC) is a rare autosomal dominant skeletal dysplasia caused by gain-of-function mutations in the parathyroid hormone receptor 1 gene, PTH1R. We report on a patient presenting in the neonatal period with clinical signs of JMC in addition to severe hypertension. A pathogenic mutation in PTH1R was demonstrated, but investigations for hypertension yielded normal results. Hypertension has not been previously associated with JMC. Given aberration of the parathyroid hormone (PTH) arathyroid-related protein pathway is the underlying pathogenic mechanism attributed to JMC, and also given evidence that hyperparathyroidism plays an important role in blood pressure homeostasis, we propose that hypertension is a hitherto unrecognized feature of JMC.
Publisher: Cambridge University Press (CUP)
Date: 21-11-2018
DOI: 10.1017/THG.2018.60
Abstract: The expansion of genetic and genomic testing in clinical practice and research and the growing market for at home personal genome testing has led to increased awareness about the impact of this form of testing on insurance. Genetic or genomic information can be requested by providers of mutually rated insurance products, who may then use it when setting premiums or determining eligibility for cover under a particular product. Australian insurers are subject to relevant legislation and an industry standard that was updated in late 2016. In 2018, the Human Genetics Society of Australasia updated its position statement on genetic testing and life insurance to account for these changes and to increase the scope of the statement to include a wider scope of insurance products that are not rated according to community risk, such as life, critical care, and income protection products. Recommendations include that providers of professional education involving genetics should include ethical, legal, and social aspects of insurance discrimination in their curricula that the Australian government take a more active role in regulating use of genetic information in personal insurance, including enacting a moratorium on use of genetic test results that information obtained in the course of a research project be excluded and that there is improved engagement between the insurance industry, regulators, and the genetics profession.
Publisher: Springer Science and Business Media LLC
Date: 15-09-2015
Publisher: MDPI AG
Date: 09-05-2014
Publisher: Springer Science and Business Media LLC
Date: 13-06-2012
Location: Australia
No related grants have been discovered for Michael Gabbett.