Mutations in the Prostaglandin Transporter SLCO2A1 Cause Primary Hypertrophic Osteoarthropathy with Digital Clubbing

Abstract

Abbreviations: HPGD, 15-hydroxyprostaglandin dehydrogenase; NMD, nonsense-mediated decay; PG, prostaglandin; PHO, hypertrophic osteoarthropathy www.jidonline.org 2473 J Busch et al.

Autoinflammatory bone disorders

“…Homozygous mutations in the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene, encoding the major enzyme responsible for prostaglandin degradation, or the solute carrier organic anion transporter family member 2A1 (SLCO2A1) gene, which encodes a prostaglandin transporter protein (PGT) responsible for intracellular prostaglandin up-take, have been identified as underlying cause [88][89][90][91][92][93][94][95]. Increased levels of circulating PGE 2 in PHO patients together with the observation, that infused PGE 2 (for therapeutic reasons in treating newborns with duct-dependent congenital heart disease) can induce skeletal changes similar to PHO, suggest that increased availability of systemic PGE 2 is responsible for the symptoms observed in PHO patients [88,91,96].…”

Identification of mutations in the prostaglandin transporter gene SLCO2A1 and its phenotype–genotype correlation in Japanese patients with pachydermoperiostosis

“…Additional manuscript for isolation of SLCO2A1 mutation in PDP patients were published [24] in revision. Fig.…”

Early‐onset inflammatory bowel disease as a model disease to identify key regulators of immune homeostasis mechanisms

“…Loss‐of‐function (LOF) mutations in the SLCO2A1 gene, encoding a prostaglandin transporter have been described to cause pediatric‐onset chronic nonspecific multiple ulcers of the small intestine, accompanied with persistent blood and protein‐losing enteropathy in the Japanese population. Mutations in SLCO2A1 have been previously reported as the cause of primary hypertrophic osteoarthropathy (PHO) . Three out of five male patients with chronic enteropathy associated with SLCO2A1 had all of the major clinical features of PHO as well, such as digital clubbing, periostosis, and pachydermia.…”