title: Identification of the Mutations in the Prostaglandin Transporter Gene, SLCO2A1 and Clinical Characterization in Korean Patients with Pachydermoperiostosis.
abstract: Pachydermoperiostosis (PDP), or primary hypertrophic osteoarthropathy, is a rare genetic disease affecting both skin and bones. Both autosomal dominant with incomplete penetrance and recessive inheritance of PDP have been previously confirmed. Recently, hydroxyprostaglandin dehydrogenase (HPGD) and solute carrier organic anion transporter family member 2A1 (SLCO2A1) were reported as pathogenic genes responsible for PDP. Both genes are involved in prostaglandin E2 (PGE2) degradation. We aimed to identify responsible genes for PDP and the clinical features in Korean patients with PDP. Six affected individuals and their available healthy family members from three unrelated Korean families with PDP were studied. All of the patients displayed complete phenotypes of PDP with finger clubbing, pachydermia, and periostosis. Mutation analysis revealed a novel heterozygous mutation in the SLCO2A1 gene at nucleotide 302 causing a substitution of the amino acid isoleucine to serine at codon 101 (p.IIe101Ser) in affected individuals. We also identified known SLCO2A1 mutations, one homozygous for c.940+1G>A, and another compound heterozygous for c.940+1G>A and c.1807C>T (p.Arg603*) from two PDP families. Genetic analyses of the PDP patients showed no abnormality in the HPGD gene. Our study further supports the role of mutations in the SLCO2A1 gene in the pathogenesis of PDP and could provide additional clues to the genotype-phenotype relations of PDP.
authors.affiliation: Department of Internal Medicine and Laboratory of Genomics and Translational Medicine, Gachon University School of Medicine, Incheon, Korea .
authors.forename: Sihoon
authors.identifier: 0000-0002-9444-5849
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul, Korea .
authors.forename: So Young
authors.identifier: 0000-0001-6002-0116
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Internal Medicine and Laboratory of Genomics and Translational Medicine, Gachon University School of Medicine, Incheon, Korea .
authors.forename: Hyun Jin
authors.identifier: 0000-0002-2936-1358
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Division of Clinical Genetics, Department of Pediatrics, Severance Children's Hospital, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea .
authors.forename: Chul-Ho
authors.identifier: 0000-0001-8045-4368
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Radiology, Woorisoa Children's Hospital, Seoul, Korea .
authors.forename: Ok-Hwa
authors.identifier: 0000-0001-5502-8746
authors.initials: OH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Endocrine Research Institute, Yonsei University College of Medicine, Seoul, Korea .
authors.forename: Yumie
authors.identifier: 0000-0003-4227-5638
authors.initials: Y
authors.lastname: Rhee
mesh_terms: D001842:Bone and Bones / Q000000981:diagnostic imaging; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000235:genetics*; D010004:Osteoarthropathy, Primary Hypertrophic / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic; D049268:Positron-Emission Tomography; D055815:Young Adult
chemical_list: D027361:Organic Anion Transporters; C503526:SLCO2A1 protein, human
keywords: Mutation; Pachydermoperiostosis; Primary Hypertrophic Osteoarthropathy; SLCO2A1 Gene