A5082227630- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Glioma Diagnosis and Treatment
- Sarcoma Diagnosis and Treatment
- Neonatal Respiratory Health Research
- Neuroblastoma Research and Treatments
- Immunodeficiency and Autoimmune Disorders
- Congenital Diaphragmatic Hernia Studies
- Diabetes and associated disorders
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Renal and related cancers
- Cancer, Hypoxia, and Metabolism
- Acute Lymphoblastic Leukemia research
- Soft tissue tumor case studies
- Neurofibromatosis and Schwannoma Cases
- Lymphoma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Tumors and Oncological Cases
- Oral and Maxillofacial Pathology
- Meningioma and schwannoma management
- Chromatin Remodeling and Cancer
- Metabolism, Diabetes, and Cancer
- Bone Tumor Diagnosis and Treatments
- Blood disorders and treatments
- Pancreatic function and diabetes
- Histiocytic Disorders and Treatments
Royal Manchester Children's Hospital
2016-2025
Brain Tumour Research
2018-2025
Manchester University NHS Foundation Trust
2017-2025
University of Manchester
2014-2022
Manchester University
2014-2022
Manchester Academic Health Science Centre
2021
St Mary's Hospital
2020
Manchester Royal Infirmary
2017
National Health Service
2014
Tameside and Glossop Integrated Care NHS Foundation Trust
2013
Heterozygous germline PTCH1 mutations are causative of Gorlin syndrome (naevoid basal cell carcinoma), but detection rates > 70% have rarely been reported. We aimed to define the in individuals with without mutations.We undertook exome sequencing on lymphocyte DNA from four unrelated families no found by Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), or RNA analysis.A heterozygous nonsense mutation SUFU was identified one exomes. 23 additional PTCH1-negative a...
STAT2 R148W impairs an essential regulatory function of STAT2, revealing the damage wreaked by excessive IFNα/β activity.
Background: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a negative immune regulator on the surface of T cells. In humans, heterozygous germline mutations in CTLA4 can cause an dysregulation syndrome. The phenotype comprises broad spectrum autoinflammatory, autoimmune, and immunodeficient features. An increased frequency malignancies primary immunodeficiencies known, but their incidence CTLA-4 insufficiency unknown. Methods: Clinical manifestations details clinical history were...
Objectives: To quantify islet cell nucleomegaly in controls and tissues obtained from patients with congenital hyperinsulinism infancy (CHI) to examine the association of proliferation. Methods: High-content analysis histologic sections serial block-face scanning electron microscopy were used nucleomegaly. Results: Enlarged nuclear areas 4.3-fold larger than unaffected nuclei, mean volume increased approximately threefold. Nucleomegaly was a normal feature pediatric islets detected regions...
Craniopharyngiomas are one of the most frequently diagnosed hypothalamo-pituitary tumors in childhood. The adamantinomatous histological subtype accounts for pediatric cases, while papillary variant is almost exclusively adults. Here, we report a case craniopharyngioma very young child, confirmed by molecular tissue analysis. A 4-year-old girl was being investigated symptomatic central hypothyroidism. Brain MR imaging revealed large solid/cystic suprasellar mass, splaying optic chiasm and...
An 11-year-old presented with bilateral renal cell carcinoma (RCC) FH-deficient RCC confirmed by immunohistochemistry. WGS no coding variants but identified a rare intronic variant in FH (c.1391-269A>G). We illustrate how combined pathological and genomic investigations enabled precise diagnosis of the underlying cause an ultra-rare clinical presentation.
We aimed to characterize mosaic populations of pancreatic islet cells from patients with atypical congenital hyperinsulinism in infancy (CHI-A) and the expression profile NKX2.2, a key transcription factor expressed β-cells but suppressed δ-cells mature pancreas.Tissue was isolated three CHI-A following subtotal pancreatectomy. diagnosed on basis mosaicism absence histopathological hallmarks focal diffuse CHI (CHI-D). Immunohistochemistry used identify quantify proportions insulin-secreting...
Congenital hyperinsulinism (CHI) causes dysregulated insulin secretion which can lead to life-threatening hypoglycaemia if not effectively managed. CHI be sub-classified into three distinct groups: diffuse, focal and mosaic pancreatic disease. Whilst the underlying of diffuse disease have been widely characterised, genetic basis is known. To gain new insights processes mosaic-CHI we studied islet tissue histopathology derived from limited surgical resection tail pancreas in a patient with...
Idiopathic CD4+ lymphocytopenia and extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma) are rare diseases in children. We report the first case a child with STK4‐ mutated who developed Epstein–Barr virus associated MALT arising salivary gland. The achieved complete remission rituximab, her immunodeficiency was cured by haematopoietic stem cell transplantation. remained well 24 months post
Abstract The glucose-6-phosphatase catalytic subunit 3 (G6PC3) encodes a ubiquitously expressed enzyme that regulates cytoplasmic glucose availability. Loss-of-function biallelic G6PC3 mutations cause severe congenital neutropenia and diverse spectrum of extra-hematological manifestations, among which inflammatory bowel disease (IBD) has been anecdotally reported. Neutrophil function clinical response to granulocyte colony-stimulating factor (G-CSF) hematopoietic stem cell transplantation...
BACKGROUND: Congenital Hyperinsulinism (CHI) is an important cause of severe and persistent hypoglycaemia in infancy childhood. The focal form (CHI-F) CHI can be potentially cured by pancreatic lesionectomy. While diagnostic characteristics CHI-F histopathology are well recognised, correlation with clinical phenotype has not been established. AIMS: We aimed to correlate the diversity profiles patients islet cell organisation tissue. METHODS: Clinical datasets were obtained from twenty-five...
Hyponatraemia is a very common electrolyte abnormality with varied presenting features depending on the underlying cause. The authors report case of 75-year-old, previously fit, gentleman who presented weight loss, lethargy and blackouts. He required four admissions to hospital over an 8-month period. Investigations revealed persistent hyponatraemia consistent diagnosis syndrome inappropriate antidiuretic hormone secretion, macrocytic anaemia partial hypopituitarism. Unfortunately, all other...
A rhabdomyomatous mesenchymal hamartoma (RMH) is a rare benign soft tissue tumour found in the face and neck region of children. three-month-old male infant was referred to our unit with polypoid anal lesion that had been present from birth. Histopathological examination excised sample showed haphazard arrangement mature striated skeletal muscle among nerves blood vessels, immunohistochemistry confirmed be RMH. There no evidence recurrence during follow-up period. This case emphasises two...
Aminoacyl tRNA synthetases/ligases (ARSs) are highly conserved enzymes involved in attaching amino acids to promoting protein synthesis. Although deficiencies of ARSs localized the mitochondria classically present with neuropathology, clinical features cytosolic ARS more variable. They have previously been associated neonatal hepatitis, but never early-onset inflammatory bowel disease.A nine-year-old Bangladeshi boy presented liver failure and deranged clotting, transaminitis cholestasis....
In Brief: The authors performed whole genome sequencing on 135 patients with congenital hyperinsulinaemia (CHI) who had negative genetic testing for previously known CHI genes. They identified nine different non-coding de novo variants (carried by 14 probands) located in a regulatory region of HK1 intron 2 that co-segregated disease families.