A5038932597- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Genomic variations and chromosomal abnormalities
- Congenital heart defects research
- RNA modifications and cancer
- Genetic Neurodegenerative Diseases
- Prenatal Screening and Diagnostics
- RNA regulation and disease
- Adolescent and Pediatric Healthcare
- Mitochondrial Function and Pathology
- Endoplasmic Reticulum Stress and Disease
- Fetal and Pediatric Neurological Disorders
- Bone health and treatments
- Attention Deficit Hyperactivity Disorder
- Rheumatoid Arthritis Research and Therapies
- Neonatal Respiratory Health Research
- Genomics and Rare Diseases
- Mesenchymal stem cell research
- NF-κB Signaling Pathways
- Cerebral Palsy and Movement Disorders
- Advanced Neuroimaging Techniques and Applications
Murdoch Children's Research Institute
2015-2024
Royal Children's Hospital
2015-2024
The University of Melbourne
2015-2024
Monash University
2005-2024
Victorian Clinical Genetics Services
2011-2019
The fragile X syndrome (FXS) is caused by silencing of the mental retardation gene (FMR1) and absence its product, protein (FMRP), resulting from CpG island methylation associated with large CGG repeat expansions (more than 200) termed full mutation (FM). We have identified a number novel epigenetic markers for FXS using matrix-assisted laser desorption/ionization-time flight mass spectrometry (MALDI-TOF MS), naming most informative X-related element 1 (FREE1) 2 (FREE2). Methylation both...
<h3>Importance</h3> Newborn screening for Angelman syndrome (AS), Prader-Willi (PWS), and chromosome 15 duplication (Dup15q) may lead to benefit from early diagnosis treatment. <h3>Objective</h3> To examine the feasibility of newborn these imprinting disorders at population scale. <h3>Design, Setting, Participants</h3> In this diagnostic study, validation data set first-tier<i>SNRPN</i>test, called methylation-specific quantitative melt analysis (MS-QMA), included 109 PWS, 48 AS, 9 Dup15q,...
Standard fragile X syndrome (FXS) diagnostic tests that target methylation of the mental retardation 1 (FMR1) CpG island 5' CGG expansion can be used to predict severity disease in males from birth, but not females.We describe specific-quantitative melt analysis (MS-QMA) targets 10 sites, with 9 within FMR1 intron 1, screen for FXS birth both sexes. The novel method combines qualitative strengths high-resolution and high-throughput, quantitative real-time PCR standard curve provide accurate...
Abstract Background Fragile X syndrome (FXS) is a common cause of intellectual disability and autism spectrum disorder (ASD) usually associated with CGG expansion, termed full mutation (FM: ≥ 200), increased DNA methylation the FMR1 promoter silencing gene. Mosaicism for presence cells either methylated FM or smaller unmethylated pre-mutation (PM: 55–199) alleles in same individual have been better cognitive functioning. This study compares age- sex-matched FM-only PM/FM mosaic individuals...
Fragile X syndrome (FXS) is a common monogenic cause of intellectual disability with autism features. While it caused by loss the
Cognitive status in females with mutations the FMR1 (fragile X mental retardation 1) gene is highly variable. A biomarker would be of value for predicting which individuals were liable to develop cognitive impairment and could benefit from early intervention. detailed analysis CpG sites bridging exon 1 intron FMR1, known as fragile X-related epigenetic element 2 (FREE2), suggests that a simple blood test identify these individuals.Study participants included 74 control (<40 CGG repeats), 62...
To examine the epigenetic basis of psychiatric symptoms and dysexecutive impairments in FMR1 premutation (PM: 55 to 199 CGG repeats) women.A total 35 PM women aged between 22 years age- IQ-matched controls (CGG <45) participated this study. All participants completed a range executive function tests self-reported disorders. The molecular measures included DNA methylation CpG island blood, presented as activation ratio (AR), 9 sites located at exon1/intron 1 boundary, size, mRNA levels.We...
FMR1 full mutations (FMs) (CGG expansion >200) in males mosaic for a normal (<45 CGG) or gray-zone (GZ) (45-54 allele can be missed with the standard 2-step fragile X syndrome (FXS) testing protocols, largely because first-line PCR tests showing GZ are not reflexed to second-line test that detect FM.We used methylation-specific quantitative melt analysis (MS-QMA) determine prevalence of cryptic FM alleles 2 independent cohorts male patients (994 from Chile and 2392 Australia) referred FXS...
Prader-Willi syndrome (PWS) and Angelman (AS) are neurodevelopmental disorders that caused by abnormal expression of imprinted genes in the 15q11-13 region. Dysregulation located this region has been proposed as a susceptibility factor for autism spectrum disorder (ASD) both disorders. This study aimed to explore symptoms ASD 25 PWS 19 AS individuals aged between 1 39 years via objective assessment. Participants completed Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2)...
To examine the interrelationships between fragile X mental retardation 1 (FMR1) mRNA and FMR1 exon 1/intron boundary methylation, white matter microstructure, executive function, in women with a premutation expansion (PM; 55-199 CGG repeats) controls (CGG < 44).Twenty PM without X-associated tremor/ataxia syndrome (FXTAS) 20 control 22 54 years of age completed this study. methylation levels for 9 CpG sites within from peripheral blood samples were analyzed. measure diffusion-weighted...
Recent evidence suggests that early changes in postural control may be discernible among females with premutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene at risk developing X-associated tremor ataxia syndrome (FXTAS). Cerebellar dysfunction is well described males and FXTAS, yet interrelationships between cerebellar volume, repeat length, FMR1 messenger RNA (mRNA) levels remain unknown. This study examined sway during standing a cohort 22 (ages...
CGG repeat expansion >200 within FMR1 , termed full mutation (FM), has been associated with promoter methylation, consequent silencing of gene expression and fragile X syndrome (FXS)—a common cause intellectual disability co‐morbid autism. Unmethylated premutation (55–199 repeats) FM alleles have related tremor/ataxia (FXTAS), a late onset neurodegenerative disorder. Here we present 33‐year‐old male FXS, white matter changes progressive deterioration in gait cerebellar signs consistent...
Methylation of the fragile X-related epigenetic element 2 (FREE2) located on exon 1/intron 1 boundary FMR1 gene is related to FMRP expression and cognitive impairment in full mutation (FM; CGG>200) individuals. We examined relationship between age, size CGG expansion methylation output ratio (MOR) at 12 CpG sites proximal using FREE2 MALDI-TOF MS. The patient cohort included 119 males 368 females, i.e. 121 healthy controls (CGG<40), 176 premutation (CGG 55–170) 190 FM 213–2000). For all...
Abstract Background Detailed analysis of imprinting center (IC) defects in individuals with Prader–Willi syndrome (PWS) is not readily available beyond chromosomal microarray (MA) analysis, and such testing important for a more accurate diagnosis recurrence risks. This the first feasibility study newly developed droplet digital polymerase chain reaction (ddPCR) examining DNA copy number differences PWS IC region those defects. Methods The cohort included 17 without 15q11‐q13 deletions or...
Abstract Chromosome 15 (C15) imprinting disorders including Prader–Willi (PWS), Angelman (AS) and chromosome duplication (Dup15q) syndromes are severe neurodevelopmental caused by abnormal expression of genes from the 15q11–q13 region, associated with DNA methylation and/or copy number changes. This study compared changes in mRNA levels UBE3A SNORD116 located within region between these their subtypes related to clinical phenotypes. The cohort included 58 participants affected a C15 disorder...
Abstract Increased intragenic DNA methylation of the Fragile X Related Epigenetic Element 2 (FREE2) in blood has been correlated with lower intellectual functioning females fragile syndrome (FXS). This study explored these relationships a paediatric cohort males FXS using Buccal Epithelial Cells (BEC). BEC were collected from 25 FXS, aged 3 to 17 years and 19 age-matched male controls without FXS. Methylation 9 CpG sites within FREE2 region was examined EpiTYPER approach. Full Scale IQ...
Although fragile X syndrome (FXS) is caused by a hypermethylated full mutation (FM) expansion with ≥200 cytosine-guanine-guanine (CGG) repeats, and decrease in FMR1 mRNA its protein (FMRP), incomplete silencing has been associated more severe autism features FXS males. This study reports on brothers (B1 B2), aged 5 2 years, autistic language delay, but higher non-verbal IQ comparison to typical FXS. CGG sizing using AmplideX PCR only identified premutation (PM: 55-199 CGGs) alleles blood....
Abstract DNA methylation of the Fragile X mental retardation 1 ( FMR1 ) exon 1/intron boundary has been associated with executive dysfunction in female carriers a premutation (PM: 55–199 CGG repeats), whereas neuroanatomical changes have PM males. To our knowledge, this study for first time examined inter-relationships between function, structure and molecular measures (DNA mRNA levels blood) control (<44 repeats) females. In group, intron was positively function cortical thickness middle...