title: Mutations in the prostaglandin transporter encoding gene SLCO2A1 cause primary hypertrophic osteoarthropathy and isolated digital clubbing.
abstract: Digital clubbing is usually secondary to different acquired diseases. Primary hypertrophic osteoarthropathy (PHO) is a rare hereditary disorder with variable digital clubbing as the most prominent feature, subperiosteal new bone formation, and arthropathy. Recently, mutations in the 15-hydroxy-prostaglandin dehydrogenase (15-PGDH) encoding gene HPGD were found to cause PHO. Here, we identified three unrelated families with different mutations in the prostaglandin transporter (PGT) encoding gene SLCO2A1 which presumably result in reduced metabolic clearance by 15-PGDH due to diminished cellular uptake of prostaglandin E(2) (PGE(2)) by mutant PGT. In two consanguineous families, homozygous mutations, an intragenic deletion that results in frameshift and a missense mutation, are associated with a severe PHO phenotype. In a third family, a heterozygous carrier of a stop mutation presents with isolated digital clubbing. Thus, our study further supports the importance of PGE(2) metabolism in the pathogenesis of digital clubbing and PHO.
authors.affiliation: Institute for Vegetative Anatomy, Charité-University Medicine of Berlin, Berlin, Germany.
authors.forename: Wenke
authors.initials: W
authors.lastname: Seifert
authors.forename: Jirko
authors.initials: J
authors.lastname: Kühnisch
authors.forename: Beyhan
authors.initials: B
authors.lastname: Tüysüz
authors.forename: Christof
authors.initials: C
authors.lastname: Specker
authors.forename: Ad
authors.initials: A
authors.lastname: Brouwers
authors.forename: Denise
authors.initials: D
authors.lastname: Horn
mesh_terms: D000328:Adult; D003241:Consanguinity; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics / Q000378:metabolism; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D027361:Organic Anion Transporters / Q000235:genetics*; D010005:Osteoarthropathy, Secondary Hypertrophic / Q000235:genetics*; D010375:Pedigree
chemical_list: D027361:Organic Anion Transporters; C503526:SLCO2A1 protein, human; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D015232:Dinoprostone