A5014431656- Genetic and rare skin diseases.
- Cutaneous Melanoma Detection and Management
- melanin and skin pigmentation
- RNA regulation and disease
- Vascular Malformations and Hemangiomas
- Tumors and Oncological Cases
- Skin and Cellular Biology Research
- Vascular Malformations Diagnosis and Treatment
- Melanoma and MAPK Pathways
- Skin Protection and Aging
- Dermatologic Treatments and Research
- Cancer and Skin Lesions
- Autoimmune Bullous Skin Diseases
- Hedgehog Signaling Pathway Studies
- Parvovirus B19 Infection Studies
- Dermatological and COVID-19 studies
- Medicine and Dermatology Studies History
- Histiocytic Disorders and Treatments
- Genomics and Rare Diseases
- Neonatal skin health care
- Wnt/β-catenin signaling in development and cancer
- Olfactory and Sensory Function Studies
- Genomic variations and chromosomal abnormalities
- Hormonal Regulation and Hypertension
- Connexins and lens biology
Great Ormond Street Hospital
2016-2025
University College London
2016-2025
The Francis Crick Institute
2019-2025
Great Ormond Street Hospital for Children NHS Foundation Trust
2014-2024
Institute of Child Health
2017-2023
Royal London Hospital
2021
Medical Research Institute
2020
University Hospital of Wales
2020
Royal Hallamshire Hospital
2020
Indiana University
2020
Senescent cells accumulate in human tissues during ageing and contribute to age-related pathologies. The mechanisms responsible for their accumulation are unclear. Here we show that senescent dermal fibroblasts express the non-classical MHC molecule HLA-E, which interacts with inhibitory receptor NKG2A expressed by NK highly differentiated CD8
Congenital melanocytic nevi (CMN) can be associated with neurological abnormalities and an increased risk of melanoma. Mutations in NRAS, BRAF, Tp53 have been described individual CMN samples; however, their role the pathogenesis multiple within same subject development features has not clear. We hypothesized that a single postzygotic mutation NRAS could responsible for individual, as well nonmelanocytic central nervous system (CNS) lesions. From 15 patients, 55 samples were sequenced after...
Sporadic vascular malformations (VMs) are complex congenital anomalies of blood vessels that lead to stroke, life-threatening bleeds, disfigurement, overgrowth, and/or pain. Therapeutic options severely limited, and multidisciplinary management remains challenging, particularly for high-flow arteriovenous (AVM).To investigate the pathogenesis sporadic intracranial extracranial VMs in 160 children which known genetic causes had been excluded, we sequenced DNA from affected tissue optimized...
Facial port‐wine stains (PWSs) are usually isolated findings; however, when associated with cerebral and ocular vascular malformations they form part of the classical triad Sturge–Weber syndrome (SWS). To evaluate associations between phenotype facial PWS diagnosis SWS in a cohort high rate SWS. Records were reviewed all 192 children seen 2011–13. Adverse outcome measures clinical (seizures, abnormal neurodevelopment, glaucoma) radiological [abnormal magnetic resonance imaging (MRI)],...
Common birthmarks can be an indicator of underlying genetic disease but are often overlooked. Mongolian blue spots (dermal melanocytosis) usually localized and transient, they extensive, permanent, associated with extracutaneous abnormalities. Co-occurrence vascular defines a subtype phakomatosis pigmentovascularis, group syndromes neurovascular, ophthalmological, overgrowth, malignant complications. Here, we discover that extensive dermal melanocytosis pigmentovascularis activating...
Mutant Pik3ca gives rise to venous malformations.
Background Congenital melanocytic naevi (CMNs) can be associated with abnormalities of the cental nervous system (CNS) and/or melanoma. Quoted incidences for these complications vary in literature, as do recommendations investigations and follow‐up.
The spectrum of central nervous system (CNS) abnormalities described in association with congenital melanocytic naevi (CMN) includes congenital, acquired, melanotic and nonmelanotic pathology. Historically, symptomatic CNS were considered to carry a poor prognosis, although studies from large centres have suggested much wider variation outcome.To establish whether routine MRI the is clinically relevant investigation children multiple CMN (more than one at birth), subclassify radiological...
The aetiology of congenital melanocytic naevi (CMNs) is unknown.To identify potential aetiological factors in families children with CMNs, and to relate these long-term outcome measures.Three hundred forty-nine CMN completed questionnaires about pregnancy parental factors, yearly on the health their child details CMN. Seventy-nine control one set questionnaires, excluding details.The mean prospective follow-up 301 was 9.2 years, median 8.9 total 2679 years. Forty per cent patients had CMNs >...
Genotype-phenotype studies can identify subgroups of patients with specific clinical features or differing outcomes, which help shape management.To characterize the frequency different causative genotypes in congenital melanocytic naevi (CMN), and to investigate genotype-phenotype genotype-outcome associations.We conducted a large cohort study we undertook MC1R genotyping from blood, high-sensitivity NRAS BRAF hotspots 156 naevus biopsies 134 CMN [male 40%; multiple 76%; projected adult size...
The treatment of congenital melanocytic naevi (CMNs) has become controversial as better data on complications have been published.To determine the longer-term risks and benefits surgery in CMNs.In this 19-year prospective study, 301 families completed yearly questionnaires about treatments CMN changes. Forty per cent CMNs were > 20 cm projected adult size (PAS) or multiple CMNs.Girls more likely to had surgical treatments. There no significant effects incidence adverse clinical outcomes,...
Congenital melanocytic nevi (CMN) are pigmented birthmarks that affect up to 80% of the skin surface area. The increased frequency CMN in families severely affected individuals is suggestive a predisposing germline genotype. We noted high prevalence red hair families, and considered role for MC1R this condition. A cohort 166 subjects underwent pigmentary phenotyping, with genotyping 113. Results were compared local control group 60 unrelated children 300 UK without CMN. had higher...
Abstract Congenital melanocytic nevi (CMN) are known to be associated with neurological abnormalities and melanoma, but have not been considered part of a developmental syndrome. The objective this study was test our clinical observation that children CMN show more facial similarities than might expected by coincidence. We selected photographs 95 white Caucasian from database only on the basis good neutral views, allowing careful evaluation morphology. These were scored independently two...
Primary melanoma of the CNS in children is extremely rare, and usually linked to congenital melanocytic naevus syndrome, caused by mosaicism for oncogenic NRAS mutations. Outcome fatal all cases. Data from murine vitro studies suggest that MEK inhibition a possible therapeutic option.Four with NRAS-mutated were treated Trametinib on compassionate basis.All four had an improvement symptoms objectively signs. These varied mild 1 month, sustained symptom-free period 9 months one case. In cases...
Azathioprine is efficacious in the treatment of severe childhood atopic dermatitis; however, robust data on adverse effects this population are lacking.We sought to assess azathioprine a pediatric dermatitis cohort, and make recommendations for monitoring based these data.Blood test results all 82 children prescribed oral our department between 2010 2012 were collated prospectively, clinical notes reviewed retrospectively.Mean age at commencing was 8.3 years (SEM 0.4). Mean maximum doses 2.4...