A5042334309- Neuroendocrine Tumor Research Advances
- Neuroblastoma Research and Treatments
- Lung Cancer Research Studies
- Cardiomyopathy and Myosin Studies
- Cardiovascular Conditions and Treatments
- RNA modifications and cancer
- Congenital heart defects research
- Genomics and Rare Diseases
- Hearing, Cochlea, Tinnitus, Genetics
- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
- Chromatin Remodeling and Cancer
- Cardiovascular Effects of Exercise
- Retinal Development and Disorders
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- interferon and immune responses
- Genetic Syndromes and Imprinting
- Genetic factors in colorectal cancer
- DNA Repair Mechanisms
- Pancreatic and Hepatic Oncology Research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Genomics and Phylogenetic Studies
- Lung Cancer Treatments and Mutations
- Genomic variations and chromosomal abnormalities
University of Auckland
2021-2025
University College London
2011-2022
Great Ormond Street Hospital
2017-2021
UCL Australia
2011
University of Liverpool
2007
University of Manchester
2007
Utrecht University
2004-2007
University of Ljubljana
2002
<h3>Background</h3> Usher syndrome (USH) is an autosomal recessive disorder comprising retinitis pigmentosa, hearing loss and, in some cases, vestibular dysfunction. It clinically and genetically heterogeneous with three distinctive clinical types (I–III) nine genes identified. This study a comprehensive genetic analysis of 172 patients evaluates the contribution digenic inheritance. <h3>Methods</h3> The <i>MYO7A, USH1C, CDH23, PCDH15, USH1G, USH2A, GPR98, WHRN, CLRN1</i> candidate gene...
Background Rare genetic conditions are frequent risk factors for, or direct causes of, paediatric intensive care unit (PICU) admission. Such frequently suspected but unidentified at PICU Compassionate and effective is greatly assisted by definitive diagnostic information. There therefore a need to provide rapid diagnosis inform clinical management. To date, whole genome sequencing (WGS) approaches have proved successful in diagnosing proportion of children with rare diseases, results may...
Primary ovarian insufficiency (POI) is a distressing cause of infertility in young women. POI heterogeneous with only few causative genes having been discovered so far. Our objective was to determine the genetic consanguineous Lebanese family two affected sisters presenting primary amenorrhoea and an absence any pubertal development. Multipoint parametric linkage analysis performed. Whole-exome sequencing done on proband. Linkage identified locus chromosome 7 where exome successfully...
The Rakeiora program was designed for high impact precision health research in Aotearoa New Zealand. It required a genomics platform to facilitate linkage of whole genome DNA sequencing data, healthcare records, and mātauranga whakapapa (genealogical knowledge) powerful, secure, transparently governed computational environment. A team Māori non-Māori with diverse professional cultural expertise co-developed Rakeiora; embedding te ao (Māori world) crucial, including principles derived from:...
Abstract Background Usher Syndrome is the leading cause of inherited deaf-blindness. It divided into three subtypes, which most common type 2, and USH2A gene accounts for 75-80% cases. Despite recent sequencing strategies, in our cohort a significant proportion individuals with 2 have just one heterozygous disease-causing mutation , or no convincing mutations across nine genes. The purpose this study was to improve molecular diagnosis these families by screening duplications, deletions...
Primary ovarian insufficiency (POI) affects 1% of women and carries significant medical psychosocial sequelae. Approximately 10% POI has a defined genetic cause, with most implicated genes relating to biological processes involved in early fetal ovary development function. Recently, Ythdc2, an RNA helicase N6-methyladenosine reader, emerged as regulator meiosis mice. Here, we describe homozygous pathogenic variants YTHDC2 3 early-onset from 2 families: c. 2567C>G, p.P856R the...
Abstract Background Primary ovarian insufficiency (POI) affects 1% of women and is associated with significant medical consequences. A genetic cause for POI can be found in up to 30% women, elucidating key roles these genes human ovary development. Objective We aimed identify the mechanism underlying early-onset 2 sisters from a consanguineous pedigree. Methods Genome sequencing variant filtering using an autosomal recessive model was performed affected their unaffected family members....
The positive regulatory (PR) domain containing 13 (PRDM13) putative chromatin modifier and transcriptional regulator functions downstream of the transcription factor PTF1A, which controls GABAergic fate in spinal cord neurogenesis hypothalamus. Here, we report a recessive syndrome associated with PRDM13 mutation. Patients exhibited intellectual disability, ataxia cerebellar hypoplasia, scoliosis, delayed puberty congenital hypogonadotropic hypogonadism (CHH). Expression studies revealed...
There is increasing evidence that vitamin B6, given either as pyridoxine or pyridoxal 5'-phosphate, can sometimes result in improved seizure control idiopathic epilepsy. Whole-exome sequencing was used to identify a de novo mutation (c.629G>A; p.Arg210His) KCNQ2 7-year-old patient whose neonatal seizures showed response and who had high plasma CSF 5'-phosphate ratio, usually indicative of an inborn error B6 metabolism. This has been described three other patients with epileptic...
Abstract Context Congenital hypopituitarism (CH) is rarely observed in combination with severe joint contractures (arthrogryposis). Schaaf-Yang syndrome (SHFYNG) phenotypically overlaps Prader-Willi syndrome, patients also manifesting arthrogryposis. L1 a group of X-linked disorders that include hydrocephalus and lower limb spasticity, presents Objective We investigated the molecular basis underlying CH arthrogryposis five patients. Patients The heterozygous p.Q666fs*47 mutation maternally...
Dilated cardiomyopathy (DCM) is a disease of the myocardium, which causes heart failure and premature death. It has been described in humans several domestic animals. In Newfoundland dog, DCM an autosomal dominant with late onset reduced penetrance. We analyzed 15 candidate genes for their involvement dog. Polymorphic microsatellite markers single Nucleotide Polymorphisms were genotyped 4 families dogs segregating dilated encoding alpha-cardiac actin (ACTC), caveolin (CAVI), cysteine-rich...
In Brief Purpose: To determine the molecular cause of sector retinitis pigmentosa and hearing loss in two affected siblings. Methods: Direct DNA sequencing USH1C gene was performed Putative pathogenic sequence changes were assayed their parent's chromosomes control chromosomes. Clinical examination included visual acuity measurement, field electrophysiologic assessment, fine matrix mapping. Retinal imaging with fundus photography, scanning laser ophthalmoscope (fundus autofluorescence),...
Abstract Objective —To evaluate the role of phospholamban gene in purebred large-breed dogs with dilated cardiomyopathy (DCM). Animals —6 DCM, including 2 Doberman Pinschers, Newfoundlands, and Great Danes. Procedure —All had clinical signs congestive heart failure, a diagnosis DCM was made on basis echocardiographic findings. Blood samples were collected from each dog, genomic DNA isolated by salt extraction method. Specific oligonucleotides designed to amplify promoter, exon 1, 5'-part...
Dilated cardiomyopathy (DCM) is a common disease of the myocardium recognized in human, dog and experimental animals. Genetic factors are responsible for large proportion cases humans, 17 genes with DCM causing mutations have been identified. The genetic origin Dobermann dogs has suggested, but no identified to date. In this paper, we describe characterization evaluation canine sarcoglycan delta (SGCD), gene implicated human hamster. Bacterial artificial chromosomes (BACs) containing SGCD...
We describe molecular diagnosis in a complex consanguineous family: four offspring presented with combinations of three distinctive phenotypes; non-syndromic hearing loss (NSHL), an unusual skeletal phenotype comprising multiple fractures, cranial abnormalities and diaphyseal expansion, significant developmental delay microcephaly. performed Chromosomal Microarray Analysis on the either or phenotypes, linkage analysis whole exome sequencing (WES) all children, parents maternal aunt....
Abstract ATP2B1 encodes plasma membrane calcium-transporting-ATPase1 and plays an essential role in maintaining intracellular calcium homeostasis that regulates diverse signaling pathways. Heterozygous de novo missense truncating variants are associated with a neurodevelopmental phenotype of variable expressivity. We describe proband distinctive craniofacial gestalt, Pierre-Robin sequence, growth deficit, periventricular heterotopia, brachymesophalangy, cutaneous syndactyly, persistent...