By using whole-exome sequencing, we identified a homozygous guanine-to-adenine transition at the invariant -1 position of the acceptor site of intron 1 (c.97-1G>A) in solute carrier organic anion transporter family member 2A1 (SLCO2A1), which encodes a prostaglandin transporter protein, as the causative mutation in a single individual with primary hypertrophic osteoarthropathy (PHO) from a consanguineous family. In two other affected individuals with PHO from two unrelated nonconsanguineous families, we identified two different compound heterozygous mutations by using Sanger sequencing. These findings confirm that SLCO2A1 mutations inactivate prostaglandin E(2) (PGE(2)) transport, and they indicate that mutations in SLCO2A1 are the pathogenic cause of PHO. Moreover, this study might also help to explain the cause of secondary hypertrophic osteoarthropathy.

Primary hypertrophic osteoarthropathy (PHO) is a rare monogenetic disease that closely mimics hypertrophic osteoarthropathy secondary to pulmonary or other pathology. The study of PHO provides an opportunity to understand both the pathogenesis of hypertrophic osteoarthropathy and the functions of the underlying genes. PHO is characterized by digital clubbing, periostosis and pachydermia. Two genes are known to be related to PHO: SLCO2A1 and HPGD. Here, we identified a recurrent heterozygous guanine-to-adenine transition at the invariant +1 position of the donor site of intron 7 (c.940+1G>A) and a novel heterozygous missense mutation p.Asn534Lys (c.1602C>A) in exon 11 of SLCO2A1 in a Chinese young man with PHO. Identification of a novel genotype in PHO will provide clues to the phenotype-genotype relations and may assist not only in the clinical diagnosis of PHO but also in the interpretation of genetic information used for prenatal diagnosis and genetic counseling.

Primary hypertrophic osteoarthropathy (PHO) is a rare monogenetic disease characterized by digital clubbing, periostosis and pachydermia. Mutations in the 15-hydroxy-prostaglandin dehydrogenase (HPGD) gene and solute carrier organic anion transporter family member 2A1 (SLCO2A1) gene have been shown to be associated with PHO. Here, we described clinical characteristics in a Chinese patient with PHO, and identified two novel mutations in SLCO2A1: a heterozygous guanine-to-thymidine transition at the invariant -1 position of the acceptor site of intron 2 (c.235-1G>T) and a heterozygous missense mutation p.Pro219Leu (c.656C>T) in exon 5.