Genetic Studies Of Pedigree Of Primary Hypertrophic Ostesarthropathy

BACKGROUND AND PURPOSEPachydermoperiostosis is a very rare monogenic hereditary osteodystrophy, also known as primary hypertrophic osteoarthropathy. Clinical features conclude clubbing,thickening of skin of head and face, osteoarthritis, and so on. Most studies suggest that it is related to hereditary factor, autosomal recessive inheritance or incomplete dominant inheritance. Currently, the studies of domestic and aborad pay close attention to the gene of 15-hydroxy prostaglandin dehydrogenase?HGPD? and prostaglandin transporter 2A1?SLCO2A1?. The encoding productions of the two genes involve the metabolism and transport of prostaglandin E2. In this study, through the genetic studies of primary hypertrophic osteoarthropathy and combine with related documents, we can further analyze the clinical features and pathogenesis of genetics.METHODSSummarizing and analyzing the clinical data of two Chinese pedigree and one sporadic case of Pachydermoperiostosis. Siphoning the blood of proband and relatives.Genomic DNA was extracted from the whole blood sample. Genetic analysis wasperformed by Sanger method after PCR of HPGD and SLCO2A1. The sequencing results were compared with the NCBI, searched for the mutations and conducted genetic analysis.RESULTS1?The proband of familiay A and his father fall inllness on the stage of teenage.The proband of familiay B fall inllness on the stage of childhood. The sporadic case C and aunt of the proband of familiay A fall inllness on the stage of youngster. Clinical manifestations conclude clubbing, sweating, seborrhea, acne, eczema, osteoarthritis,but did not have thickening of skin of head and face. Laboratory tests did not have obvious abnormalities. The X-ray of some patients showed periosteal reaction,cortical thickening and acral osteolysis.2 ? Through the all exon sequencing of HPGD and SLCO2A1, we found the heterozygous mutation in family A, c.173₁74delCT, which located in the second exon of HPGD; While, We found one heterozygous mutation in the the family A,c.941-1G>A,which located in the gene of SLCO2A1. We found the homozygous mutation in proband of family B, c.310₃11del CT, which located in the third exon of HPGD. We found two heterozygous mutations in the the sporadic cases C, c.464G>A and c.1117C>T, which located in the gene of SLCO2A1.CONCLUSIONS1 ? The heterozygous mutation, c.173₁74delCT?p.Thr58ThrfsX9?, is new frameshift mutation of HPGD. The heterozygous mutations, c.464G>A?p.Cys155Tyr?and c.1117C>T?p.Leu373Phe?, which are new missense mutation of SLCO2A1. The heterozygous mutations, c.941-1G>A, which is a spite mutation.2?The structure of 15-hydroxy prostaglandin dehydrogenase take in change due to the mutation of HPGD. While, The structure of prostaglandin transporter have a change owe to the mutation of SLCO2A1.