A5102006451- Genomics and Rare Diseases
- Genetic factors in colorectal cancer
- Genomic variations and chromosomal abnormalities
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- American Constitutional Law and Politics
- Quantum Mechanics and Applications
- Cystic Fibrosis Research Advances
- Blood disorders and treatments
- Immunodeficiency and Autoimmune Disorders
- Telomeres, Telomerase, and Senescence
- Cold Atom Physics and Bose-Einstein Condensates
- CRISPR and Genetic Engineering
- American History and Culture
- Lysosomal Storage Disorders Research
- Bone Metabolism and Diseases
- European Cultural and National Identity
- Machine Learning in Bioinformatics
- Trypanosoma species research and implications
- Protein Tyrosine Phosphatases
- DNA and Biological Computing
- Craniofacial Disorders and Treatments
- Moyamoya disease diagnosis and treatment
- Cancer, Lipids, and Metabolism
- Childhood Cancer Survivors' Quality of Life
Oxford University Hospitals NHS Trust
2015-2023
University of Oxford
2016-2023
John Radcliffe Hospital
2023
Nuffield Orthopaedic Centre
2022
Churchill Hospital
2016-2021
William Harvey Research Institute
2021
National Institute for Health Research
2019-2021
University of Birmingham
2021
Centre for Human Genetics
2016-2019
Oxford BioMedica (United Kingdom)
2019
The translation of genome sequencing into routine health care has been slow, partly because concerns about affordability. aspirational cost a is $1000, but there little evidence to support this estimate. We estimate the using in clinical patients with cancer or rare diseases.We performed microcosting study Illumina-based UK National Health Service laboratory processing 399 samples/year. Cost data were collected for all steps pathway, including bioinformatics analysis and reporting results....
<h3>Background</h3> Craniosynostosis, the premature fusion of one or more cranial sutures, occurs in ∼1 2250 births, either isolation as part a syndrome. Mutations at least 57 genes have been associated with craniosynostosis, but only minority these are included routine laboratory genetic testing. <h3>Methods</h3> We used exome whole genome sequencing to seek cause cohort 40 subjects selected by clinical molecular geneticists being high-priority cases, and whom prior clinically driven...
Abstract Background Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, diagnostic yields many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25–30%. This part because although entire genomes sequenced, analysis confined to silico gene panels or coding regions genome. Methods We undertook WGS on cohort 122 unrelated disease and their relatives (300 genomes) who had been pre-screened by...
Curry-Jones syndrome (CJS) is a multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas. Cerebellar medulloblastoma has been described in single affected individual; another, biopsy of lesions showed features trichoblastoma. The combination asymmetric clinical features, manifestations, neoplastic association previously led...
Over 150 different proteins attach to the plasma membrane using glycosylphosphatidylinositol (GPI) anchors. Mutations in 18 genes that encode components of GPI-anchor biogenesis result a phenotypic spectrum includes learning disability, epilepsy, microcephaly, congenital malformations and mild dysmorphic features. To determine incidence defects, we analysed exome data from 4293 parent-child trios recruited Deciphering Developmental Disorders (DDD) study. All probands had neurodevelopmental...
PurposeApproaches to secondary findings in genome sequencing (GS) are unresolved. In the United Kingdom, GS is now routinely available through 100,000 Genomes Project, which offers participants feedback of limited findings.MethodsIn Oxford, a Genomic Medicine Multidisciplinary Team (GM-MDT) governs local access GS, and reviews findings. Semistructured interviews were conducted with 19 GM-MDT members explore perspectives on findings.ResultsWhile enthusiastic about for diagnosing rare disease,...
During the past several years, use of computer programs in analysis protein and DNA sequences has become commonplace.In all but simplest procedures, ability to critically review results obtained with methods requires i ) a basic knowledge algorithms employed (and assumptions upon which they are based), ii) an awareness capabilities limitations particular program that implements algorithm, iii) some familiarity probability statistics.We describe number have been applied apolipoprotein...
Noonan syndrome (NS) is characterised by distinctive facial features, heart defects, variable degrees of intellectual disability and other phenotypic manifestations. Although the mode inheritance typically dominant, recent studies indicate LZTR1 may be associated with both dominant recessive forms. Seeking to describe characteristics LZTR1-associated NS, we searched for likely pathogenic variants using two approaches. First, scrutiny exomes from 9624 patients recruited Deciphering...
Minichromosome maintenance protein 10 (MCM10) is essential for eukaryotic DNA replication. Here, we describe compound heterozygous MCM10 variants in patients with distinctive, but overlapping, clinical phenotypes: natural killer (NK) cell deficiency (NKD) and restrictive cardiomyopathy (RCM) hypoplasia of the spleen thymus. To understand mechanism MCM10-associated disease, modeled these human lines. causes chronic replication stress that reduces viability due to increased genomic instability...
Objectives: To retrospectively evaluate the incidence of palliative care (PC) consultations for older adults with lung cancer who died in past five years, as well impact social determinants health (SDOHs) on PC consultations.Sample & Setting: 63 participants aged 65 years or a diagnosis years. Electronic records were used to extract data.Methods Variables: A medical record extraction form was collect following data: (a) diagnosis, (b) consultations, (c) patient demographic information, and...
A multi-disciplinary approach to promote engagement, inform decision-making and support clinicians patients is increasingly advocated realise the potential of genome-scale sequencing in clinic for patient benefit. Here we describe results establishing a genomic medicine team (GM-MDT) case selection, processing, interpretation return results. We report consecutive series 132 (involving 10 medical specialties with 43.2% cases having neurological disorder) undergoing exome over 10-month period...
A novel familial arrhythmia syndrome, cardiac ryanodine receptor (RyR2) calcium release deficiency syndrome (CRDS), has recently been described. We evaluated a large and well characterized family to assess provocation testing, risk factor stratification response therapy in CRDS.We present with multiple unheralded sudden deaths aborted arrests, primarily children young adults, no clear phenotype on standard clinical testing.Genetic analysis, including whole genome sequencing, firmly...
Abstract Background Genomics enables individualized diagnosis and treatment, but large challenges remain to functionally interpret rare variants. To date, only one causative variant has been described for KCNK9 imprinting syndrome (KIS). The genotypic phenotypic spectrum of KIS yet be the precise mechanism disease fully understood. Methods This study discovers mechanisms underlying (KIS) by describing 15 novel alterations from 47 KIS-affected individuals. We use clinical genetics...
Whole-exome/whole-genome sequencing (WES/WGS) has the potential to enhance genetic diagnosis of rare disease, and is increasingly becoming part routine clinical care in mainstream medicine. Effective translation will require ongoing efforts a number areas including: selection appropriate patients, provision effective consent, pre- post-test counselling, improving variant interpretation algorithms practices, management secondary findings including those found incidentally actively sought....
Abstract Mendelian disorders in glucose-6-phosphate metabolism can present with inflammatory bowel disease [IBD]. Using whole genome sequencing we identified a homozygous variant the glucose-6-phosphatase G6PC3 gene [c.911dupC; p.Q305fs*82] an adult patient congenital neutropenia, lymphopenia and childhood-onset, therapy-refractory Crohn’s disease. Because is expressed several haematopoietic non-haematopoietic cells it was unclear whether allogeneic stem cell transplantation [HSCT] would...
The UK 100,000 Genomes Project offered participants screening for additional findings (AFs) in genes associated with familial hypercholesterolemia (FH) or hereditary cancer syndromes including breast/ovarian (HBOC), Lynch, adenomatous polyposis, MYH-associated multiple endocrine neoplasia (MEN), and von Hippel-Lindau. Here, we report disclosure processes, manifestation of AF-related disease, outcomes, costs.
Loss-of-function mutations in DOCK8 are linked to hyper-IgE syndrome. Patients typically present with recurrent sinopulmonary infections, severe cutaneous viral food allergies and elevated serum IgE. Although patients may a spectrum of disease-related symptoms, molecular mechanisms explaining phenotypic variability poorly defined. Here we characterized novel compound heterozygous mutation patient diagnosed primary combined immunodeficiency which was not typical classical deficiency. In...
Journal Article William Henry Seward: Lincoln's Right Hand. By John M. Taylor. (New York: HarperCollins, 1991. xii + 340 pp. $25.00, ISBN 0-06-016307-0.) Get access Adrian Cook University of Reading, England Search for other works by this author on: Oxford Academic Google Scholar American History, Volume 79, Issue 2, September 1992, Page 666, https://doi.org/10.2307/2080105 Published: 01 1992
The aim of this study was to identify the causative mutation in a family with an unusual presentation autosomal dominant osteopetrosis (OPT), proximal renal tubular acidosis (RTA), stones, epilepsy, and blindness, combination features not previously reported. We undertook exome sequencing one affected unaffected member, followed by targeted analysis known candidate genes mutation. This identified missense (c.643G>A; p.Gly215Arg) gene encoding chloride/proton antiporter 7 (gene CLCN7 ,...
A procedure is described for the precise nonrelativistic evaluation of dipole polarizabilities ${\mathrm{H}}_{2}^{+}$ and ${\mathrm{D}}_{2}^{+}$ that avoids any approximation based on size electron mass relative to nucleus mass. The constructed so sum rules may be used assess accuracy calculation. resulting are consistent with experiment within error bars measurements far more than values obtained by other theoretical methods.
ABSTRACT Minichromosome maintenance protein 10 (Mcm10) is essential for eukaryotic DNA replication. Here, we describe compound heterozygous MCM10 mutations in patients with distinctive but overlapping clinical phenotypes – natural killer (NK) cell deficiency (NKD) and restrictive cardiomyopathy (RCM) hypoplasia of the spleen thymus. To understand mechanism Mcm10-associated disease, modeled these human lines. Mcm10 causes chronic replication stress that reduces viability due to increased...