Prostaglandin transporter mutations cause pachydermoperiostosis with myelofibrosis.

Human Mutation
Christine P DiggleDavid T Bonthron

Abstract

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 E(2) (PGE(2)) 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 PGE(2), but unlike HPGD-deficient patients, also excreted considerable quantities of the PGE(2) 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....Continue Reading

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Citations

Jan 25, 2013·Frontiers of Medicine·Zeng ZhangZhenlin Zhang
Feb 2, 2013·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Henner MorbachHermann J Girschick
Jun 16, 2014·Journal of Dermatological Science·H NiizekiJ Kudoh
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Mar 20, 2013·The Journal of Clinical Endocrinology and Metabolism·Zeng ZhangZhen-Lin Zhang
Mar 2, 2019·International Journal of Molecular Sciences·Xabier Elorza-VidalRaúl Estévez
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Jun 6, 2021·The Journal of Investigative Dermatology·Mami IshibashiKenji Kabashima

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