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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

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.
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Figure 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.

Mentions: The case of this family (Fig. 1 and 2A-C) has been previously reported (11). The 56-year-old proband, who was born to healthy non-consanguineous parents, visited the clinic for genetic counseling of his son. At 19 years of age, the proband presented with enlarged hands and feet, knee joints swelling and pain and was then referred to a neurosurgeon for suspicion of acromegaly. He underwent hypophysectomy, which showed no tumor lesion in the specimen. Attention was aroused only after periosteal thickening was observed in the skeletal survey of the hands and forearm bones, indicating primary hypertrophic osteoarthropathy as well as facial furrowing. His two brothers, who were also diagnosed as PDP, showed similar clinical features to the proband.


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)

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

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

Figure 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.
Mentions: The case of this family (Fig. 1 and 2A-C) has been previously reported (11). The 56-year-old proband, who was born to healthy non-consanguineous parents, visited the clinic for genetic counseling of his son. At 19 years of age, the proband presented with enlarged hands and feet, knee joints swelling and pain and was then referred to a neurosurgeon for suspicion of acromegaly. He underwent hypophysectomy, which showed no tumor lesion in the specimen. Attention was aroused only after periosteal thickening was observed in the skeletal survey of the hands and forearm bones, indicating primary hypertrophic osteoarthropathy as well as facial furrowing. His two brothers, who were also diagnosed as PDP, showed similar clinical features to the proband.

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