A5044649471- Genetics and Neurodevelopmental Disorders
- Epilepsy research and treatment
- Genomics and Rare Diseases
- Metabolism and Genetic Disorders
- Glycogen Storage Diseases and Myoclonus
- Diet and metabolism studies
- Lysosomal Storage Disorders Research
- Genomic variations and chromosomal abnormalities
- Hedgehog Signaling Pathway Studies
- Amino Acid Enzymes and Metabolism
- Cellular transport and secretion
- Genetic Neurodegenerative Diseases
- Infectious Encephalopathies and Encephalitis
- CRISPR and Genetic Engineering
- Renal and related cancers
- Fetal and Pediatric Neurological Disorders
- RNA modifications and cancer
- Bacterial Infections and Vaccines
- Neuroscience and Neuropharmacology Research
- Neurological diseases and metabolism
- Cystic Fibrosis Research Advances
- Pharmacological Effects and Toxicity Studies
- Vascular Malformations Diagnosis and Treatment
- Thyroid and Parathyroid Surgery
- Nuclear Structure and Function
The University of Melbourne
2015-2025
Austin Health
2015-2025
Royal Children's Hospital
2016-2022
Murdoch Children's Research Institute
2018-2022
Walter and Eliza Hall Institute of Medical Research
2022
Austin Hospital
2018-2019
Monash University
2018
Florey Institute of Neuroscience and Mental Health
2016-2018
Hertie Institute for Clinical Brain Research
2018
The Royal Melbourne Hospital
2018
We performed hypothesis-free linkage analysis and exome sequencing in a family with two siblings who had neuronal ceroid lipofuscinosis (NCL). Two peaks maximum LOD scores of 3.07 2.97 were found on chromosomes 7 17, respectively. Unexpectedly, we these to be homozygous for c.813_816del (p.Thr272Serfs∗10) mutation the progranulin gene (GRN, granulin precursor) latter peak. Heterozygous mutations GRN are major cause frontotemporal lobar degeneration TDP-43 inclusions (FTLD-TDP), second most...
Abstract Objective: We examined whether glucose transporter 1 (GLUT1) deficiency causes common idiopathic generalized epilepsies (IGEs). Methods: The IGEs are common, heritable that usually follow complex inheritance; currently little is known about their genetic architecture. Previously considered rare, GLUT1 deficiency, due to mutations in SLC2A1 , leads failure of transport across the blood–brain barrier and inadequate for brain metabolism. was first associated with an encephalopathy more...
To determine if a significant proportion of patients with myoclonic-astatic epilepsy (MAE) have glucose transporter 1 (GLUT1) deficiency.Genetic analysis.Ambulatory and hospitalized care.Eighty-four unrelated probands MAE were phenotyped SLC2A1 was sequenced analyzed by multiplex ligation-dependent probe amplification. Any identified mutations then screened in controls.Any mutations.Four 84 had mutation on sequencing. Multiplex amplification analysis did not reveal any genomic rearrangements...
<h3>Objective:</h3> Following our original description of generalized epilepsy with febrile seizures plus (GEFS+) in 1997, we analyze the phenotypic spectrum 409 affected individuals 60 families (31 new families) and expand GEFS+ spectrum. <h3>Methods:</h3> We performed detailed electroclinical phenotyping on all available family members. Genetic analysis known genes was carried out where possible. compared genetic data to those published literature over last 19 years. <h3>Results:</h3>...
Kufs disease, an adult-onset neuronal ceroid lipofuscinosis, is challenging to diagnose and genetically heterogeneous. Mutations in CLN6 were recently identified recessive disease presenting as progressive myoclonus epilepsy (Type A), whereas the molecular basis of cases with dementia motor features B) unknown. We performed genome-wide linkage mapping two families Type B a single region on chromosome 11 which both showed linkage. Exome sequencing five samples from homozygous compound...
Glucose transporter 1 (GLUT1) deficiency caused by mutations of SLC2A1 is an increasingly recognized cause genetic generalized epilepsy. We previously reported that >10% (4 34) a cohort with early onset absence epilepsy (EOAE) had GLUT1 deficiency. This study uses new 55 patients EOAE to confirm finding. Patients typical seizures beginning before 4 years age were screened for solute carrier family 2 (facilitated glucose transporter), member (SLC2A1) or deletions. All spike-waves on...
Abstract Brain somatic mutations are an increasingly recognized cause of epilepsy, brain malformations and autism spectrum disorders may be a hidden other neurodevelopmental neurodegenerative disorders. At present, mosaicism can detected only in the rare situations autopsy or biopsy. Liquid biopsy using cell-free DNA derived from cerebrospinal fluid has malignant tumours. Here, we asked if liquid used to detect non-malignant diseases. First, reliably quantified 28 patients with focal...
Abstract Relatively little is known about the neurobiological basis of speech disorders although genetic determinants are increasingly recognized. The first gene for primary disorder was FOXP2 , identified in a large, informative family with verbal and oral dyspraxia. Subsequently, many de novo familial cases severe associated mutations have been reported. These include sequencing alterations, translocations, uniparental disomy, genomic copy number variants. We studied eight probands their...
Abstract Febrile seizures represent the most common type of pathological brain activity in young children and are influenced by genetic, environmental developmental factors. In a minority cases, febrile precede later development epilepsy. We conducted genome-wide association study 7635 cases 83 966 controls identifying replicating seven new loci, all with P &lt; 5 × 10−10. Variants at two loci were functionally related to altered expression fever response genes PTGER3 IL10, four other...
We report development of a targeted resequencing gene panel for focal epilepsy, the most prevalent phenotypic group epilepsies.The was designed using molecular inversion probe (MIP) capture technology and sequenced massively parallel Illumina sequencing.We demonstrated proof principle that mutations can be detected in 4 previously genotyped epilepsy cases. searched both germline somatic 251 patients with unsolved sporadic or familial identified 11 novel very rare missense variants 5...
We studied a consanguineous Palestinian Arab family segregating an autosomal recessive progressive myoclonus epilepsy (PME) with early ataxia. PME is rare, often fatal syndrome, initially responsive to antiepileptic drugs which over time becomes refractory and can be associated cognitive decline. Linkage analysis was performed the disease locus narrowed chromosome 19p13.3. Fourteen candidate genes were screened by conventional Sanger sequencing in one, LMNB2, novel homozygous missense...
Abstract Febrile seizures (FS) are the most common seizure syndrome and potentially a prelude to more severe epilepsy. Although zinc (Zn 2+ ) metabolism has previously been implicated in FS, whether or not variation proteins essential for Zn homeostasis contributes susceptibility is unknown. Synaptic co-released with glutamate modulates neuronal excitability. SLC30A3 encodes transporter 3 (ZNT3), which primarily responsible moving into synaptic vesicles. Here we sequenced discovered rare...
To critically re-evaluate cases diagnosed as adult neuronal ceroid lipofuscinosis (ANCL) in order to aid clinicopathologic diagnosis a route further gene discovery.Through establishment of an international consortium we pooled 47 unsolved regarded by referring centers ANCL. Clinical and neuropathologic experts within the Consortium established diagnostic criteria for ANCL based on literature assess each case. A panel 3 neuropathologists independently reviewed source pathologic data. Cases...
Two unrelated families were ascertained in which sisters had infantile onset of epilepsy and developmental delay. Mutations the protocadherin 19 (PCDH19) gene cause mental retardation limited to females (EFMR). Despite both sister pairs having a PCDH19 mutation, neither parent each family was heterozygous carrier mutation. The possibility parental mosaicism mutations investigated.Genomic DNA from peripheral blood obtained sequenced for mutations. Parentage confirmed by markers.Both have...
Genetic epilepsy with febrile seizures plus (GEFS+) is a familial syndrome characterized by heterogeneous phenotypes ranging from mild disorders such as to epileptic encephalopathies (EEs) Dravet (DS). Although DS often occurs de novo SCN1A pathogenic variants, milder GEFS+ spectrum are associated inherited variants. We identified seven cases non-EE and including monozygotic twin pair. Febrile (FS+) occurred in six patients, five of whom had additional seizure types. The remaining case...
Summary The availability of glucose, and its glycolytic product lactate, for cerebral energy metabolism is regulated by specific brain transporters. Inadequate delivery leads to neurologic impairment. Haploinsufficiency the glucose transporter GLUT 1 causes a characteristic early onset encephalopathy, has recently emerged as an important cause variety childhood or later‐onset generalized epilepsies paroxysmal exercise‐induced dyskinesia. We explored whether mutations in genes encoding other...
To determine whether the GNAQ R183Q mutation is present in forme fruste cases of Sturge-Weber syndrome (SWS) to establish a definitive molecular diagnosis.We used sensitive droplet digital PCR (ddPCR) detect and quantify tissues from epilepsy surgery 4 patients with leptomeningeal angiomatosis; none had ocular or cutaneous manifestations.Low levels were detected brain tissue all cases-ranging 0.42% 7.1% frequency-but not blood-derived DNA. Molecular evaluation confirmed diagnosis 1 case...
Kufs disease is the major adult form of neuronal ceroid lipofuscinosis, but rare and difficult to diagnose. Diagnosis was traditionally dependent on demonstration characteristic storage material, distinction from normal age-related accumulation lipofuscin can be challenging. Mutation CLN6 has emerged as most important cause recessive but, remarkably, also responsible for variant late infantile lipofuscinosis. Here we provide a detailed description due pathogenic variants. We studied 20 cases...