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

Takashi Sasaki, Hironori Niizeki, Atsushi Shimizu, Aiko Shiohama, Asami Hirakiyama, Torayuki Okuyama, Atsuhito Seki, Kenji Kabashima, Atsushi Otsuka, Akira Ishiko, Keiji Tanese, Shun Ichi Miyakawa, Jun Ichi Sakabe, Masamitsu Kuwahara, Masayuki Amagai, Hideyuki Okano, Makoto Suematsu, Jun Kudo

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)


Background: Pachydermoperiostosis (PDP) is a rare genetic disorder characterized by 3 major symptoms: pachydermia including cutis verticis gyrata (CVG), periostosis, and finger clubbing. Recently, a homozygous mutation in the gene HPGD, which encodes 15-hydroxyprostaglandin dehydrogenase (15-PGDH), was found to be associated with PDP. However, mutations in HPGD have not been identified in Japanese PDP patients. Objective: We aimed to identify a novel responsible gene for PDP using whole exome sequencing by next-generation DNA sequencer (NGS). Methods: Five patients, including 2 patient-parent trios were enrolled in this study. Entire coding regions were sequenced by NGS to identify candidate mutations associated with PDP. The candidate mutations were subsequently sequenced using the Sanger method. To determine clinical characteristics, we analyzed histological samples, as well as serum and urinary prostaglandin E2 (PGE2) levels for each of the 5 PDP patients, and 1 additional patient with idiopathic CVG. Results: From initial analyses of whole exome sequencing data, we identified mutations in the solute carrier organic anion transporter family, member 2A1 (. SLCO2A1) gene, encoding prostaglandin transporter, in 3 of the PDP patients. Follow-up Sanger sequencing showed 5 different SLCO2A1 mutations (c.940+1G>A, p.E427_P430del, p.G104*, p.T347I, p.Q556H) in 4 unrelated PDP patients. In addition, the splice-site mutation c.940+1G>A identified in 3 of 4 PDP patients was determined to be a founder mutation in the Japanese population. Furthermore, it is likely that the combination of these SLCO2A1 mutations in PDP patients is also associated with disease severity. Conclusion: We found that SLCO2A1 is a novel gene responsible for PDP. Although the SLCO2A1 gene is only the second gene discovered to be associated with PDP, it is likely to be a major cause of PDP in the Japanese population.

Original languageEnglish
Pages (from-to)36-44
Number of pages9
JournalJournal of Dermatological Science
Issue number1
Publication statusPublished - 2012 Oct


  • CVG
  • Mutation analysis
  • NGS
  • PDP
  • PGT
  • Prostaglandin transporter
  • SLCO2A1
  • SNP
  • Whole exome sequencing

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology


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