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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 - J. Korean Med. Sci. (2016)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine and Laboratory of Genomics and Translational Medicine, Gachon University School of Medicine, Incheon, Korea .

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.

No MeSH data available.


Related in: MedlinePlus

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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Figure 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.

Mentions: PCR was performed for screening of SLCO2A1 and HPGD mutations followed by a direct sequence analysis, and no HPGD mutation was found in affected individuals. The results of these genetic analyses are shown in Fig. 3.


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 - J. Korean Med. Sci. (2016)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835599&req=5

Figure 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.
Mentions: PCR was performed for screening of SLCO2A1 and HPGD mutations followed by a direct sequence analysis, and no HPGD mutation was found in affected individuals. The results of these genetic analyses are shown in Fig. 3.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine and Laboratory of Genomics and Translational Medicine, Gachon University School of Medicine, Incheon, Korea .

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.

No MeSH data available.


Related in: MedlinePlus