J Korean Med Sci.  2016 May;31(5):735-742. 10.3346/jkms.2016.31.5.735.

Identification of the Mutations in the Prostaglandin Transporter Gene, SLCO2A1 and Clinical Characterization in Korean Patients with Pachydermoperiostosis

• Lee S
• Park SY
• Kwon HJ
• Lee CH
• Kim OH
• Rhee Y

• KMID: 2373671
• DOI: http://doi.org/10.3346/jkms.2016.31.5.735

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.

Keyword

Pachydermoperiostosis; Primary Hypertrophic Osteoarthropathy; SLCO2A1 Gene; Mutation

MeSH Terms

Bone and Bones/diagnostic imaging
Child, Preschool
DNA Mutational Analysis
Exons
Heterozygote
Humans
Male
Middle Aged
Organic Anion Transporters/*genetics
Osteoarthropathy, Primary Hypertrophic/diagnostic imaging/*genetics/pathology
Pedigree
Phenotype
Polymorphism, Genetic
Positron-Emission Tomography
Young Adult
Organic Anion Transporters

Figure

• 

  Fig. 1 Pedigrees of affected individuals with SLCO2A1 mutations. In the pedigree, arrows indicate the proband. Filled black, patients with PDP; Half-black, healthy members with a heterozygous mutation; Gray, healthy members not doing genotyping test.

• 

  Fig. 2 Clinical features of affected individuals with SLCO2A1 mutations. (A-C) Clinical pictures of family 1 proband. (A) Thickening and furrowing of the facial skin. (B-C) Digital clubbing and swelling of the ankle joint. (D-H) Clinical pictures of family 2 proband. (D) Thickening and greasiness of facial skin. (E) Digital clubbing. (F-G) Cortical hyperostosis of long bones. (H) Diffusely increased uptake in the whole axial and appendicular long bones shown by whole body bone scan. (I-J) 18F-fluoride PET scan images of femur and tibia show increased cortical/periosteal uptake in the proband of family 3.

• 

  Fig. 3 Localization and sequence chromatogram of identified SLCO2A1 mutations. Upper: The positions of the mutations in the exons of SLCO2A1 in this study. Lower: SLCO2A1 mutations in PDP families. family 1, (A) c.302T>G; family 2, (B) c.940+1G>A and (C) c.1807C>T; family 3, (C) c.940+1G>A.

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