A5053065182- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Language Development and Disorders
- Congenital heart defects research
- Prenatal Screening and Diagnostics
- Chromosomal and Genetic Variations
- Hedgehog Signaling Pathway Studies
- Fetal and Pediatric Neurological Disorders
- DNA Repair Mechanisms
- Renal and related cancers
- Tuberous Sclerosis Complex Research
- CRISPR and Genetic Engineering
- RNA regulation and disease
- Renal cell carcinoma treatment
- Neurobiology of Language and Bilingualism
- Polyomavirus and related diseases
- Histiocytic Disorders and Treatments
- Neurogenetic and Muscular Disorders Research
- Epilepsy research and treatment
- Reading and Literacy Development
- Biomedical Research and Pathophysiology
- Assisted Reproductive Technology and Twin Pregnancy
- Autism Spectrum Disorder Research
- Genetic Associations and Epidemiology
Murdoch Children's Research Institute
2008-2024
Victorian Clinical Genetics Services
2008-2023
Royal Children's Hospital
2005-2022
The University of Melbourne
2005-2022
Walter and Eliza Hall Institute of Medical Research
2020-2022
Services Australia
2022
Hôpital Necker-Enfants Malades
2017
Sorbonne Université
2017
Institut de Neurobiologie de la Méditerranée
2008
Inserm
2008
<h3>Objective</h3> Determining the genetic basis of speech disorders provides insight into neurobiology human communication. Despite intensive investigation over past 2 decades, etiology most in children remains unexplained. To test hypothesis that have a etiology, we performed analysis with severe disorder, specifically childhood apraxia (CAS). <h3>Methods</h3> Precise phenotyping together research genome or exome were on referred primary diagnosis CAS. Gene coexpression and gene set...
Periventricular heterotopia (PH) is an etiologically heterogeneous disorder characterized by nodules of neurons ectopically placed along the lateral ventricles. Most affected patients have seizures and their cognitive level varies from normal to severely impaired. At present, two genes been identified cause PH when mutated. Mutations in FLNA (Xq28) ARFGEF2 (20q13) are responsible for X-linked bilateral a rare autosomal recessive form with microcephaly. Chromosomal rearrangements involving...
Bloom syndrome is a recessive human genetic disorder with features of genome instability, growth deficiency and predisposition to cancer. The only known causative gene the BLM helicase that member protein complex along topoisomerase III alpha, RMI1 2, which maintains replication fork stability dissolves double Holliday junctions prevent instability. Here we report identification second gene, RMI2, deleted in affected siblings Bloom-like features. Cells from homozygous individuals exhibit...
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,...
Summary Objective To investigate the significance of variation in ADGRV 1 (also known as GPR 98 , MASS and VLGR ), MEF 2C other genes at 5q14.3 chromosomal locus myoclonic epilepsy. Methods We studied epilepsy phenotypes 4 individuals with deletion found that all had seizures. then screened 6 contiguous 5q14.3, 2C, CETN 3 MBLAC 2 POLR 3G LYSMD a 95‐patient cohort Of these genes, point mutations cause phenotype involving seizures intellectual disability. A role for has been proposed...
The 2-hit model of genetic disease is well established in cancer, yet has only recently been reported to cause brain malformations associated with epilepsy. Pathogenic germline and somatic variants genes the mechanistic target rapamycin (mTOR) pathway have implicated several cortical development. We investigated by performing analysis searching for mTOR related pathways.We searched pathogenic 2 brothers drug-resistant focal epilepsy surgically resected dysplasia (FCD) type IIA. Exome...
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%)...
SUMMARY Variable expressivity of disease-associated variants implies a role for secondary that modify clinical features. We assessed the effects modifier towards outcomes 2,252 individuals with primary variants. Among 132 families 16p12.1 deletion, distinct rare and common variant classes conferred risk specific developmental features, including short tandem repeats neurological defects SNVs microcephaly, while additional multiple genetic diagnoses. Within disease population cohorts 773 we...
Speech disorders are highly prevalent in the preschool years, but frequently resolve. The neurobiological basis of most persistent and severe form, apraxia speech, remains elusive. Current neuroanatomical models speech processing adults propose two parallel streams. dorsal stream is involved sound to motor transformations, while ventral supports sound/letter meaning. Data-driven theories on role these streams during atypical language development lacking. Here we provide comprehensive...
Hypothalamic hamartoma with gelastic seizures is a well-established cause of drug-resistant epilepsy in early life. The development novel surgical techniques has permitted the genomic interrogation hypothalamic tissue. This revealed causative mosaic variants within GLI3, OFD1 and other key regulators sonic-hedgehog pathway minority cases. Sonic-hedgehog signalling proteins localize to cellular organelle primary cilia. We therefore explored hypothesis that cilia gene may underlie hitherto...
The introduction of molecular techniques in conjunction with classical cytogenetic methods has recent years greatly improved the diagnostic potential for chromosomal abnormalities. In particular, microarray–comparative genomic hybridization (CGH) based on use BAC clones promises a sensitive strategy detection DNA copy-number changes genomewide scale, offering resolution as high >30,000 “bands” (as defined by number BACs within currently highest-density array) [Ishkanian et al., 2004]. We...
Abstract Neurexin 1 gene ( NRXN1 ) deletions are associated with several neurodevelopmental disorders. Communication difficulties have been reported, yet no study has examined specific speech and language features of individuals deletions. Here, we characterized phenotypes in 21 children (14 families), aged 1.8–17 years, Deletions ranged from 74 to 702 kb consisted mostly either exons 1–3 or 1–5. Speech sound disorders were frequent (69%), although few severe. The majority (57%) had...
Abstract We aimed to determine whether SNP-microarray genomic testing of saliva had a greater diagnostic yield than blood for pathogenic copy number variants (CNVs). selected patients who underwent CMA both and from 23,289 21,857 samples. Our cohort comprised 370 individuals both, 224 with syndromic intellectual disability (ID) 146 isolated ID. Mosaic CNVs or aneuploidy were detected in but not 20/370 (4.4%). All 20 ID, accounting 9.1% the ID sub-cohort. Pathogenic large size (median 46 Mb),...
Abstract 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 ascertained 70 unrelated probands clinical diagnosis performed trio genome sequencing. Our bioinformatic analysis examined nucleotide, indel, copy number, structural short...
Abstract The spondylocostal dysostoses (SCD) are a clinically and genetically heterogeneous group of disorders characterized by defects vertebral segmentation rib abnormalities. We report on the diagnosis two siblings with SCD. Diagnosis was first made in female infant following pregnancy that complicated early fetal hydrops nuchal translucency 8.2 mm trimester. clinical picture co‐existent confined placental mosaicism (CPM) for tetrasomy 9p. To our knowledge, this is CPM Postnatally SCD...
Abstract We aimed to determine whether SNP-microarray genomic testing of saliva had a greater diagnostic yield than blood for pathogenic copy number variants (CNVs). selected patients who underwent CMA both and from 23,289 21,857 samples. Our cohort comprised 370 individuals both, 224 with syndromic intellectual disability (ID) 146 isolated ID. Mosaic CNVs or aneuploidy were detected in but not 20/370 (4.4%). All 20 ID, accounting 9.1% the ID sub-cohort. Pathogenic large size (median 46 Mb),...