A5015465800- Pharmacogenetics and Drug Metabolism
- Pharmaceutical studies and practices
- Viral Infections and Vectors
- Health Systems, Economic Evaluations, Quality of Life
- Neonatal and Maternal Infections
- Trypanosoma species research and implications
- Growth Hormone and Insulin-like Growth Factors
- Genomics and Rare Diseases
- Thyroid Disorders and Treatments
- Sleep and related disorders
- Antiplatelet Therapy and Cardiovascular Diseases
- Diabetes Management and Research
- Drug Solubulity and Delivery Systems
- Diabetes and associated disorders
- Vector-Borne Animal Diseases
- SARS-CoV-2 and COVID-19 Research
- Mosquito-borne diseases and control
- Antibiotics Pharmacokinetics and Efficacy
- Genetics and Neurodevelopmental Disorders
- Genetic Associations and Epidemiology
- Iron Metabolism and Disorders
- Neonatal Respiratory Health Research
- BRCA gene mutations in cancer
- Adrenal Hormones and Disorders
- Neuroendocrine Tumor Research Advances
Manchester University NHS Foundation Trust
2015-2025
University of Manchester
2013-2025
St Mary's Hospital
2017-2025
St Mary's Hospital
2017-2025
St. Mary's Hospital
2017-2025
Genomics (United Kingdom)
2021-2025
Connolly Hospital Blanchardstown
2015-2024
Royal College of Surgeons in Ireland
2012-2024
Manchester University
2024
St. Mary’s Hospital
2024
Mucopolysaccharidosis type IIIA (MPSIIIA) is a lysosomal storage disorder caused by mutations in N-sulfoglucosamine sulfohydrolase (SGSH), resulting heparan sulfate (HS) accumulation and progressive neurodegeneration. There are no treatments. We previously demonstrated improved neuropathology MPSIIIA mice using lentiviral vectors (LVs) overexpressing SGSH wild-type (WT) hematopoietic stem cell (HSC) transplants (HSCTs), achieved via donor monocyte/microglial engraftment the brain. However,...
CTP:phosphoethanolamine cytidylyltransferase (ET), encoded by PCYT2, is the rate-limiting enzyme for phosphatidylethanolamine synthesis via CDP-ethanolamine pathway. Phosphatidylethanolamine one of most abundant membrane lipids and particularly enriched in brain. We identified five individuals with biallelic PCYT2 variants clinically characterized global developmental delay regression, spastic para- or tetraparesis, epilepsy progressive cerebral cerebellar atrophy. Using patient fibroblasts...
Aminoglycosides are widely used antibiotics with notable side effects, such as nephrotoxicity, vestibulotoxicity, and sensorineural hearing loss (cochleotoxicity). MT‐RNR1 is a gene that encodes the 12s rRNA subunit mitochondrial homologue of prokaryotic 16s rRNA. Some variants (i.e., m.1095T>C; m.1494C>T; m.1555A>G) more closely resemble bacterial result in increased risk aminoglycoside‐induced loss. Use aminoglycosides should be avoided individuals an variant associated unless...
Aminoglycosides are commonly prescribed antibiotics used for the treatment of neonatal sepsis. The MT-RNR1 m.1555A>G variant predisposes to profound aminoglycoside-induced ototoxicity (AIO). Current genotyping approaches take several days, which is unfeasible in acute settings. To develop a rapid point-of-care test (POCT) before implementation this technology setting guide antibiotic prescribing and avoid AIO. This pragmatic prospective trial recruited neonates admitted 2 large intensive...
Nicotinamide adenine dinucleotide (NAD) is essential for embryonic development. To date, biallelic loss-of-function variants in 3 genes encoding nonredundant enzymes of the NAD de novo synthesis pathway - KYNU, HAAO, and NADSYN1 have been identified humans with congenital malformations defined as deficiency disorder (CNDD). Here, we 13 further individuals predicted to be damaging, phenotypes ranging from multiple severe complete absence malformation. Enzymatic assessment variant...
Although regular exercise is a critical component of the management type 2 diabetes, many patients do not meet their targets. Lack associated with obesity and adverse cardiovascular outcomes.We aimed to assess habits in obese Irish diabetes determine if are adhering guidelines identify perceived barriers this group.A cross-sectional study attending routine outpatient clinics at our institution, public teaching hospital located on outskirts Dublin City.A total 145 were administered...
Mucopolysaccharidosis IIIB is a paediatric lysosomal storage disease caused by deficiency of the enzyme α-N-acetylglucosaminidase (NAGLU), involved in degradation glycosaminoglycan heparan sulphate. Absence NAGLU leads to accumulation partially degraded sulphate within lysosomes and extracellular matrix, giving rise severe CNS degeneration with progressive cognitive impairment behavioural problems. There are no therapies. Haematopoietic stem cell transplant shows great efficacy related...
Hypogonadism, usually hypogonadotropic in origin, is the most common nondiabetic endocrinopathy hereditary hemochromatosis (HH). Early studies, evaluating small numbers of patients with advanced HH, report prevalence rates 10-100%. The clinical presentation HH has changed recent years as a result increased awareness and screening. We assessed hypogonadism large group diagnosed single center over past 20 yr, period follow-up spanning time before after widespread screening was introduced HFE...
PurposeA few de novo missense variants in the cytoplasmic FMRP-interacting protein 2 (CYFIP2) gene have recently been described as a novel cause of severe intellectual disability, seizures, and hypotonia 18 individuals, with p.Arg87 substitutions majority.MethodsWe assembled data from 19 newly identified all previously published individuals CYFIP2 variants. By structural modeling investigation WAVE-regulatory complex (WRC)-mediated actin polymerization six patient fibroblast lines we...
Understanding the effectiveness of infection control methods in reducing and preventing SARS-CoV-2 transmission healthcare settings is high importance. We sequenced genomes for patients workers (HCWs) across multiple geographically distinct UK hospitals, obtaining 173 high-quality genomes. integrated patient movement staff location data into analysis viral genome to understand spatial temporal dynamics transmission. identified eight contact clusters (PCC) with significantly increased...
Several healthcare organizations have developed pre-emptive pharmacogenetic testing programs, where is undertaken prior to the prescription of a medicine. This review characterizes barriers and facilitators which influenced development these programs. A bidirectional citation searching strategy identified relevant publications before standardized data extraction approach was applied. Publications were grouped by program synthesis using Consolidated Framework for Implementation Research...
Rationale: Despite the increased recognition of TBX4 (T-BOX transcription factor 4)-associated pulmonary arterial hypertension (PAH), genotype–phenotype associations are lacking and may provide important insights. Objectives: To compile functionally characterize all variants reported to date undertake a comprehensive genotype-phenotype analysis. Methods: We assembled multicenter cohort 137 patients harboring monoallelic assessed pathogenicity missense variation (n = 42) using novel...
Pharmacogenetics can impact patient care and outcomes through personalizing the selection of medicines, resulting in improved efficacy a reduction harmful side effects. Despite existence compelling clinical evidence international guidelines highlighting benefits pharmacogenetics practice, implementation within National Health Service United Kingdom is limited. An important barrier to overcome development IT solutions that support integration pharmacogenetic data into health systems. This...
Abstract South Asians develop type 2 diabetes (T2D) early in life and often with normal body mass index (BMI). However, reasons for this are poorly understood because genetic research is largely focused on European ancestry groups. We used recently derived multi-ancestry partitioned polygenic scores (pPSs) to elucidate underlying etiological pathways British Pakistani Bangladeshi individuals T2D ( n = 11,678) gestational mellitus (GDM) 1,965) the Genes & Health study 50,556). Beta cell...