Dorothy Halliday
A5005135322- Neurofibromatosis and Schwannoma Cases
- Meningioma and schwannoma management
- Vascular Malformations Diagnosis and Treatment
- Bone Tumor Diagnosis and Treatments
- Connective tissue disorders research
- Cardiac Valve Diseases and Treatments
- Protease and Inhibitor Mechanisms
- Aortic Disease and Treatment Approaches
- Genetic factors in colorectal cancer
- Orbital Angular Momentum in Optics
- Chromatin Remodeling and Cancer
- Metamaterials and Metasurfaces Applications
- Sarcoma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Gastrointestinal Tumor Research and Treatment
- Prostate Cancer Treatment and Research
- Cancer, Hypoxia, and Metabolism
- Bone health and treatments
- BRCA gene mutations in cancer
- Terahertz technology and applications
- Prostate Cancer Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Genomics and Rare Diseases
- Cancer-related gene regulation
- Particle Accelerators and Free-Electron Lasers
Oxford Centre for Computational Neuroscience
2018-2024
Oxford University Hospitals NHS Trust
2015-2024
Science Oxford
2019-2024
University of Oxford
2004-2022
Nuffield Orthopaedic Centre
2017-2022
John Radcliffe Hospital
2009-2022
Queen Alexandra Hospital
2022
Moorfields Eye Hospital NHS Foundation Trust
2022
National Health Service
2022
Bristol Royal Infirmary
2022
PurposeBy incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) establish Legius syndrome (LGSS).MethodsWe used a multistep process, beginning with Delphi method involving global experts subsequently non-NF experts, patients, foundations/patient advocacy groups.ResultsWe reached consensus on minimal clinical genetic diagnosing differentiating NF1 LGSS, which have phenotypic overlap...
Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) men with germline BRCA1/2 mutations.
Neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) are genetically distinct tumor predisposition syndromes with overlapping phenotypes. We sought to update the diagnostic criteria for NF2 SWN by incorporating recent advances in genetics, ophthalmology, neuropathology, neuroimaging.We used a multistep process, beginning Delphi method involving global disease experts subsequently non-neurofibromatosis clinical experts, patients, foundations/patient advocacy groups.We reached consensus on...
From a large series of 1009 probands with pathogenic FBN1 mutations, data for 320 patients <18 years age at the last follow-up evaluation were analyzed (32%). At time diagnosis, median was 6.5 years. examination, population classified as follows: neonatal Marfan syndrome, 14%; severe 19%; classic 32%; probable 35%. Seventy-one percent had ascending aortic dilation, 55% ectopia lentis, and 28% major skeletal system involvement. Even when complications existed in childhood, rates surgery...
AimsIn patients with Marfan syndrome and other type-1 fibrillinopathies, genetic testing is becoming more easily available, leading to the identification of mutations early in course disease. This study evaluates cardiovascular (CV) risk associated discovery a fibrillin-1 (FBN1) mutation.
Objectives Schwannomatosis is a dominantly inherited condition predisposing to schwannomas of mainly spinal and peripheral nerves with some diagnostic overlap neurofibromatosis-2 (NF2), but the underlying epidemiology poorly understood. We present birth incidence prevalence allowing for NF2. Methods NF2 cases were ascertained from Manchester region England (population=4.8 million) across UK. Point calculated regional statistics. Genetic analysis was also performed on , LZTR1 SMARCB1 blood...
<h3>Background</h3> The clinical severity of disease in neurofibromatosis type 2 (NF2) is variable. Patients affected with a constitutional truncating <i>NF2</i> mutation have severe disease, while missense mutations or mosaic present milder attenuated phenotype. Genotype-derived natural history data are important to inform discussions on prognosis and management. <h3>Methods</h3> We assessed NF2 phenotype 142 patients relation the UK Genetic Severity Score validate its use as research...
We aimed to determine the proportion of individuals in our schwannomatosis cohort whose disease is associated with an LZTR1 mutation.We used exome sequencing, Sanger and copy number analysis screen 65 unrelated who were negative for a germline NF2 or SMARCB1 mutation. also screened samples from 39 patients unilateral vestibular schwannoma (UVS), plus at least one other schwannoma, but did not have identifiable mosaic identified mutations 6 16 (37.5%) had affected relative, 11 49 (22%)...
Germline pathogenic variants in the E-cadherin gene (CDH1) are strongly associated with development of hereditary diffuse gastric cancer. There is a paucity data to guide risk assessment and management families cancer that do not carry CDH1 variant, making it difficult make informed decisions about surveillance risk-reducing surgery. We aimed identify new candidate genes predisposition affected without variants.
To evaluate the incidence of mosaicism in de novo neurofibromatosis 2 (NF2).Patients fulfilling NF2 criteria, but with no known affected family member from a previous generation (n = 1055), were tested for variants lymphocyte DNA and where available tumor DNA. The proportion individuals proven or presumed mosaic variant was assessed allele frequencies identified evaluated using next-generation sequencing.The rate proven/presumed 232/1055 (22.0%). However, nonmosaic heterozygous pathogenic...
Lynch syndrome is a rare familial cancer caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging increase risk of early-onset aggressive prostate The IMPACT study prospectively assessing prostate-specific antigen (PSA) screening men with germline variants. Here, we report usefulness PSA screening, incidence, tumour characteristics after first round...
<h3>Background</h3> Meningiomas have been reported to occur in approximately 50% of neurofibromatosis type 2 (NF2) patients. The <i>NF2</i> gene is commonly biallelically inactivated both schwannomas and meningiomas. spectrum mutations consists mainly truncating (nonsense frameshift) mutations. A smaller number patients missense mutations, which are associated with a milder disease phenotype. <h3>Methods</h3> This study analysed the cumulative incidence gender effects as well...
<h3>Background:</h3> The diagnosis of Marfan syndrome (MFS) is usually initially based on clinical criteria according to the number major and minor systems affected following international nosology. <i>FBN1</i> mutation carriers, at risk aortic complications who would not be properly diagnosed only grounds, growing importance owing increased availability molecular screening. aim study was identify patients should considered for <h3>Methods:</h3> Our series included 1009 probands with a known...
<h3>Background</h3> Neurofibromatosis 2 (NF2) is an autosomal-dominant tumour predisposition syndrome characterised by bilateral vestibular schwannomas, considerable morbidity and reduced life expectancy. Although genotype–phenotype correlations are well established in NF2, little known about effects of mutation type or location within the gene on mortality. Improvements NF2 diagnosis management have occurred, but their effect patient survival unknown. <h3>Methods</h3> We evaluated clinical...
Abstract Background NF2 patients develop multiple nervous system tumors including bilateral vestibular schwannomas (VS). The and their surgical treatment are associated with deafness, neurological disability, mortality. Medical bevacizumab has been reported to reduce VS growth improve hearing. In addition evaluating these effects, this study also aimed determine other important consequences of patient-reported quality life the impact on rates. Methods Patients treated underwent serial...
Abstract Background Radiation treatment of benign tumors in tumor predisposition syndromes is controversial, but short-term studies from centers suggest safety despite apparent radiation-associated malignancy being reported. We determined whether radiation NF2-related schwannomatosis patients associated with increased rates subsequent (M)/malignant progression (MP). Methods All UK NF2 were eligible if they had a clinical/molecular diagnosis. Cases treated for tumors. Controls matched...
Objectives New diagnostic criteria for NF2-related schwannomatosis (NF2) were published in 2022. An updated UK prevalence was generated accordance with these, an emphasis on the rate of de novo NF2 (a 50% frequency is widely quoted genetic counselling). The distribution variant types among and familial cases also assessed. Methods National database identifies patients meeting from a highly ascertained population cared by England’s specialised service. Diagnostic assessed 1 February 2023....
Purpose:To identify genetic etiologies and genotype/phenotype associations for unsolved ocular congenital cranial dysinnervation disorders (oCCDDs). Methods:We coupled phenotyping with exome or genome sequencing of 467 probands (550 affected 1108 total individuals) genetically oCCDDs, integrating analyses pedigrees, human animal model phenotypes, de novo variants to rare candidate single nucleotide variants, insertion/deletions, structural disrupting protein-coding regions.Prioritized were...
Evans DG, Raymond FL, Barwell JG, Halliday D. Genetic testing and screening of individuals at risk NF2. management the at‐risk individual for neurofibromatosis type 2 (NF2) is complicated by well‐documented mosaicism that causes a milder later onset more asymmetrical disease course. Risks NF2 were derived from genetic over 1000 through Manchester NF2‐testing service. Individuals are or have ‘potential’ if they features fall short diagnostic criteria first‐degree relative someone with...
Advances in molecular biology have resulted novel therapy for neurofibromatosis 2-related (NF2) tumours, highlighting the need robust outcome measures. The disease-focused NF2 impact on quality of life (NFTI-QOL) patient questionnaire was assessed as an measure treatment a multi-centre study. NFTI-QOL related to clinician-rated severity (ClinSev) and genetic (GenSev) over repeated visits. Data were evaluated 288 patients (n = 464 visits) attending English national clinics from 2010 2012....
Mutations in the human fibrillin 1 gene (FBN1) cause Marfan syndrome (MFS), an autosomal dominant connective tissue disorder. Knowledge about FBN1 mutations is important for early diagnosis, management, and genetic counseling. However, mutation detection a challenge because very large size ( approximately 200 kb) 350 detected so far are scattered over 65 exons. Conventional methods large-scale of expensive, technically demanding, or time consuming. Recently, high-capacity low-cost method was...
ARX mutations are associated with variable clinical phenotypes. We report a new neurodegenerative phenotype known mutation and causing early abnormal neurodevelopment, complex movement disorder, infantile epileptic encephalopathy suppression-burst pattern (Ohtahara syndrome). A male infant presented at age 5 months dyskinetic which was initially diagnosed as spasms. Clinical deterioration accompanied by progressive cortical atrophy reduction in white matter volume resulting death the first...