These two authors contributed equally to this work.
Mutations in the prostaglandin transporter encoding gene SLCO2A1 Cause primary hypertrophic osteoarthropathy and isolated digital clubbing†
Article first published online: 24 FEB 2012
© 2012 Wiley Periodicals, Inc.
Special Issue: Focus on the NIH Undiagnosed Diseases Program
Volume 33, Issue 4, pages 660–664, April 2012
How to Cite
Seifert, W., Kühnisch, J., Tüysüz, B., Specker, C., Brouwers, A. and Horn, D. (2012), Mutations in the prostaglandin transporter encoding gene SLCO2A1 Cause primary hypertrophic osteoarthropathy and isolated digital clubbing. Hum. Mutat., 33: 660–664. doi: 10.1002/humu.22042
Communicated by Ravi Savarirayan
- Issue published online: 12 MAR 2012
- Article first published online: 24 FEB 2012
- Accepted manuscript online: 13 FEB 2012 12:00AM EST
- Manuscript Accepted: 19 JAN 2012
- Manuscript Received: 10 NOV 2011
- digital clubbing;
- primary hypertrophic osteoarthropathy
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 E2 (PGE2) 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 PGE2 metabolism in the pathogenesis of digital clubbing and PHO. Hum Mutat 33:660–664, 2012. © 2012 Wiley Periodicals, Inc.