ORCID Profile
0000-0002-9048-2044
Current Organisations
St. James's Hospital
,
Trinity College Dublin
,
Children's Health Ireland
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Publisher: Elsevier BV
Date: 2021
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.JID.2016.07.034
Abstract: Blue rubber bleb nevus syndrome (Bean syndrome) is a rare, severe disorder of unknown cause, characterized by numerous cutaneous and internal venous malformations gastrointestinal lesions are pathognomonic. We discovered somatic mutations in TEK, the gene encoding TIE2, in 15 of 17 in iduals with blue rubber bleb nevus syndrome. Somatic mutations were also identified in five of six in iduals with sporadically occurring multifocal venous malformations. In contrast to common unifocal venous malformation, which is most often caused by the somatic L914F TIE2 mutation, multifocal forms are predominantly caused by double (cis) mutations, that is, two somatic mutations on the same allele of the gene. Mutations are identical in all lesions from a given in idual. T1105N-T1106P is recurrent in blue rubber bleb nevus, whereas Y897C-R915C is recurrent in sporadically occurring multifocal venous malformation: both cause ligand-independent activation of TIE2, and increase survival, invasion, and colony formation when expressed in human umbilical vein endothelial cells.
Publisher: Springer Science and Business Media LLC
Date: 04-01-2009
DOI: 10.1038/NG.276
Abstract: Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant form of genetic hair loss. In a large Chinese family carrying MUHH, we identified a pathogenic initiation codon mutation in U2HR, an inhibitory upstream ORF in the 5' UTR of the gene encoding the human hairless homolog (HR). U2HR is predicted to encode a 34-amino acid peptide that is highly conserved among mammals. In 18 more families from different ancestral groups, we identified a range of defects in U2HR, including loss of initiation, delayed termination codon and nonsense and missense mutations. Functional analysis showed that these classes of mutations all resulted in increased translation of the main HR physiological ORF. Our results establish the link between MUHH and U2HR, show that fine-tuning of HR protein levels is important in control of hair growth, and identify a potential mechanism for preventing hair loss or promoting hair removal.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 11-2013
Publisher: Elsevier BV
Date: 09-2020
Publisher: Oxford University Press (OUP)
Date: 28-01-2018
DOI: 10.1111/BJD.15928
Publisher: American Medical Association (AMA)
Date: 04-2021
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.JAAD.2017.06.042
Abstract: Although most patients with atopic dermatitis (AD) are effectively managed with topical medication, a significant minority require systemic therapy. Guidelines for decision making about advancement to systemic therapy are lacking. To guide those considering use of systemic therapy in AD and provide a framework for evaluation before making this therapeutic decision with the patient. A subgroup of the International Eczema Council determined aspects to consider before prescribing systemic therapy. Topics were assigned to expert reviewers who performed a topic-specific literature review, referred to guidelines when available, and provided interpretation and expert opinion. We recommend a systematic and holistic approach to assess patients with severe signs and symptoms of AD and impact on quality of life before systemic therapy. Steps taken before commencing systemic therapy include considering alternate or concomitant diagnoses, avoiding trigger factors, optimizing topical therapy, ensuring adequate patient/caregiver education, treating coexistent infection, assessing the impact on quality of life, and considering phototherapy. Our work is a consensus statement, not a systematic review. The decision to start systemic medication should include assessment of severity and quality of life while considering the in idual's general health status, psychologic needs, and personal attitudes toward systemic therapies.
Publisher: Springer Science and Business Media LLC
Date: 04-10-2023
Publisher: Elsevier BV
Date: 07-2020
Publisher: BMJ
Date: 12-07-2019
DOI: 10.1136/JMEDGENET-2019-106024
Abstract: Capillary malformation-arteriovenous malformation is an autosomal dominant disorder, characterised by capillary malformations and increased risk of fast-flow vascular malformations, caused by loss-of-function mutations in the RASA1 or EPHB4 genes. Around 25% of the patients do not seem to carry a germline mutation in either one of these two genes. Even if other genes could be involved, some in iduals may have mutations in the known genes that escaped detection by less sensitive techniques. We tested the hypothesis that mosaic mutations could explain some of previously negative cases. DNA was extracted from peripheral blood lymphocytes, saliva or vascular malformation tissues from four patients. RASA1 and EPHB4 coding regions and exon/intron boundaries were analysed by targeted custom gene panel sequencing. A second panel and/or Sanger sequencing were used to confirm the identified mutations. Four distinct mosaic RASA1 mutations, with an allele frequency ranging from 3% to 25%, were identified in four index patients with classical capillary malformation-arteriovenous malformation phenotype. Three mutations were known, one was novel. In one patient, a somatic second hit was also identified. One index case had three affected children, illustrating that the mosaicism was also present in the germline. This study shows that RASA1 mosaic mutations can cause capillary malformation-arteriovenous malformation. Thus, highly sensitive sequencing techniques should be considered as diagnostic tools, especially for patients with no family history. Even low-level mosaicism can cause the classical phenotype and increased risk for offspring. In addition, our study further supports the second-hit pathophysiological mechanism to explain the multifocality of vascular lesions in this disorder.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 06-2021
Publisher: Springer Science and Business Media LLC
Date: 06-2009
DOI: 10.1038/NG0609-762B
Publisher: Oxford University Press (OUP)
Date: 04-12-2019
DOI: 10.1111/BJD.18643
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Alan Irvine.