A5019332282- Genetic and Kidney Cyst Diseases
- Renal and related cancers
- Protist diversity and phylogeny
- Cystic Fibrosis Research Advances
- Biomedical Research and Pathophysiology
- Genetic Syndromes and Imprinting
- Fetal and Pediatric Neurological Disorders
- Pediatric Urology and Nephrology Studies
- Prenatal Screening and Diagnostics
- Congenital heart defects research
- Autism Spectrum Disorder Research
- Genetics and Neurodevelopmental Disorders
Newcastle University
2018-2025
University of Newcastle Australia
2020
Centre for Life
2018-2019
Significance The treatment of genetic kidney disease is challenging, as this requires both the correction underlying gene defect and delivery treatment. Here we show that by using antisense oligonucleotides, can induce exon skipping a mutated in CEP290 , within renal epithelial cells derived from patient with ciliopathy syndrome called Joubert syndrome. This rescues truncated protein to near full-length restores ciliary phenotype. In Cep290 murine model syndrome, achievable systemic an...
Significance Our current understanding of genetic disease is often inadequate, largely due to background effects that modify presentation. This particularly challenging for rare diseases lack sufficient numbers patients genome-wide association studies. We show in a series experiments using murine model Joubert syndrome, multisystem ciliopathy, single locus modifier cystic kidney disease. go on the human homolog plays similar role cohort patients. These findings make significant contribution...
Abstract Joubert syndrome (JBTS) is an incurable multisystem ciliopathy syndrome. The most commonly mutated gene in JBTS patients with a cerebello-retinal-renal phenotype CEP290 (alias JBTS5 ). encoded protein localises to the proximal end of primary cilium, transition zone, where it controls ciliary composition and signalling. We examined cilium structure fibroblast cells derived from homozygous compound heterozygous nonsense mutations show that elongation cilia, impaired ciliogenesis...
Nephronophthisis-related ciliopathies (NPHP-RC) are a group of inherited genetic disorders that share defect in the formation, maintenance or functioning primary cilium complex, causing progressive cystic kidney disease and other clinical manifestations. Mutations centrosomal protein 164 kDa (CEP164), also known as NPHP15, have been identified cause NPHP-RC. Here we utilised MRC-Wellcome Trust Human Developmental Biology Resource (HDBR) to perform immunohistochemistry studies on human...
Ciliopathies may be classed as primary or motile depending on the underlying ciliary defect and are usually considered distinct clinical entities. Primary ciliopathies associated with multisystem syndromes typically affecting brain, kidney, eye, well other organ systems such liver, skeleton, auditory system, metabolism. Motile a heterogenous group of disorders defects in specialised ciliated tissues found within lung, reproductive dyskinesia, bronchiectasis, infertility rarely hydrocephalus....
Abstract Background Joubert syndrome and related disorders (JSRD) Jeune are multisystem ciliopathy with overlapping phenotypes. There a growing number of genetic causes for these rare syndromes, including the recently described genes ARL3 CEP120 . Methods We sought to explore developmental expression patterns in humans gain additional understanding conditions. used an RNA situ detection technique called RNAscope characterise human embryos foetuses collaboration MRC-Wellcome Trust Human...
<b>Background:</b><i>CEP164</i> encodes a centrosomal protein required for assembly of primary cilia. More recently it has been suggested may also have role in formation multiple motile Pathogenic variants <i>CEP164</i> are known to cause nephronophthisis-related ciliopathies but a causative link the ciliopathy ciliary dyskinesia (PCD) not proven. <b>Aim:</b> To assess airway cilia patient with clinical history consistent PCD, and bi-allelic <i>CEP164</i>. Method: A bronchiectasis...
Abstract Background: Joubert syndrome and related disorders (JSRD) Jeune are multisystem ciliopathy with overlapping phenotypes. There a growing number of genetic causes for these rare syndromes, including the recently described genes ARL3 CEP120 . Methods: We sought to explore developmental expression patterns in humans gain additional understanding conditions. used an RNA situ detection technique called RNAscope characterise human embryos foetuses collaboration MRC-Wellcome Trust Human...
Abstract Joubert syndrome and related disorders (JSRD) Jeune are multisystem ciliopathy with overlapping phenotypes. There a growing number of genetic causes for these rare syndromes, including the recently described genes ARL3 CEP120 . We sought to explore developmental expression patterns in humans gain additional understanding conditions. used an RNA situ detection technique called RNAscope characterise human embryos foetuses collaboration MRC-Wellcome Trust Human Developmental Biology...
Abstract Background: Joubert syndrome and related disorders (JSRD) Jeune are multisystem ciliopathy with overlapping phenotypes. There a growing number of genetic causes for these rare syndromes, including the recently described genes ARL3 CEP120 . Methods: We sought to explore developmental expression patterns in humans gain additional understanding conditions. used an RNA situ detection technique called RNAscope characterise human embryos foetuses collaboration MRC-Wellcome Trust Human...