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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Prostaglandin transporter mutations cause pachydermoperiostosis with myelofibrosis
Human Mutation, Volume 33, No. 8, Year 2012
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Description
Pachydermoperiostosis, or primary hypertrophic osteoarthropathy (PHO), is an inherited multisystem disorder, whose features closely mimic the reactive osteoarthropathy that commonly accompanies neoplastic and inflammatory pathologies. We previously described deficiency of the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (HPGD) as a cause of this condition, implicating elevated circulating prostaglandin E2 (PGE2) as causative of PHO, and perhaps also as the principal mediator of secondary HO. However, PHO is genetically heterogeneous. Here, we use whole-exome sequencing to identify recessive mutations of the prostaglandin transporter SLCO2A1, in individuals lacking HPGD mutations. We performed exome sequencing of four probands with severe PHO, followed by conventional mutation analysis of SLCO2A1 in nine others. Biallelic SLCO2A1 mutations were identified in 12 of the 13 families. Affected individuals had elevated urinary PGE2, but unlike HPGD-deficient patients, also excreted considerable quantities of the PGE2 metabolite, PGE-M. Clinical differences between the two groups were also identified, notably that SLCO2A1-deficient individuals have a high frequency of severe anemia due to myelofibrosis. These findings reinforce the key role of systemic or local prostaglandin excess as the stimulus to HO. They also suggest that the induction or maintenance of hematopoietic stem cells by prostaglandin may depend upon transporter activity. © 2012 Wiley Periodicals, Inc.
Authors & Co-Authors
Diggle, Christine P.
United Kingdom, Leeds
University of Leeds
Parry, David A.
United Kingdom, Leeds
University of Leeds
Logan, Clare V.
United Kingdom, Leeds
University of Leeds
Laissue, Paul
Colombia, Bogota
Universidad Del Rosario
Colombia, Bogota
Genética Molecular de Colombia
Rivera, Carolina
Colombia, Bogota
Universidad Del Rosario
Restrepo, Carlos Martín
Colombia, Bogota
Universidad Del Rosario
Colombia, Bogota
Genética Molecular de Colombia
Fonseca, Dora J.
Colombia, Bogota
Universidad Del Rosario
Colombia, Bogota
Genética Molecular de Colombia
Morgan, Joanne E.
United Kingdom, Leeds
University of Leeds
Allanore, Yannick
France, Paris
Université Paris Cité
Fontenay, Michaela
France, Paris
Cnrs Centre National de la Recherche Scientifique
Wipff, Julien
France, Paris
Université Paris Cité
Varret, Mathilde
France, Paris
Hôpital Bichat-claude-bernard Ap-hp
Gibault, Laure
France, Paris
Hopital Cochin Ap-hp
France, Paris
Université Paris Cité
Dalantaeva, Nadezhda
United Kingdom, London
Barts and the London School of Medicine and Dentistry
Russian Federation, Moscow
Ministry of Health of Russian Federation
Korbonits, Márta
United Kingdom, London
Barts and the London School of Medicine and Dentistry
Zhou, Bowen
China, Wuhan
Jianghan University
Yuan, Gang
China, Wuhan
Tongji Medical College of Huazhong University of Science and Technology
Harifi, Ghita
Morocco, Marakech
Mohammed Vi University Medical Center
Cefle, Kivanc
Turkey, Istanbul
İstanbul Tıp Fakültesi
Palanduz, Sukru
Turkey, Istanbul
İstanbul Tıp Fakültesi
Akoglu, Hadim
Turkey, Ankara
Ankara Numune Education and Research Hospital
Zwijnenburg, Petra J.
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Lichtenbelt, Klaske D.
Netherlands, Utrecht
University Medical Center Utrecht
Aubry-Rozier, Bérengère
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Superti-Furga, Andrea
Switzerland, Lausanne
Université de Lausanne Unil
Dallapiccola, Bruno
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
Accadia, Maria
Italy, Lecce
Ospedale Vito Fazzi
Brancati, Francesco
Italy, Chieti
University of G. D'annunzio Chieti and Pescara
Italy, San Giovanni Rotondo
Irccs Casa Sollievo Della Sofferenza
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Sheridan, Eamonn G.
United Kingdom, Leeds
University of Leeds
Taylor, Graham Roy
United Kingdom, Leeds
University of Leeds
Carr, Ian M.
United Kingdom, Leeds
University of Leeds
Johnson, Colin A.
United Kingdom, Leeds
University of Leeds
Markham, Alexander F.
United Kingdom, Leeds
University of Leeds
Bonthron, David T.
United Kingdom, Leeds
University of Leeds
Statistics
Citations: 74
Authors: 34
Affiliations: 23
Identifiers
Doi:
10.1002/humu.22111
ISSN:
10597794
e-ISSN:
10981004
Research Areas
Cancer
Genetics And Genomics