title: Mutations in the SLCO2A1 gene and primary hypertrophic osteoarthropathy: a clinical and biochemical characterization.
abstract: BACKGROUND
  We previously demonstrated that deficiency of the prostaglandin transporter (SLCO2A1) is a cause of primary hypertrophic osteoarthropathy (PHO). However, its clinical and metabolic characteristics have not been well defined.
  
  
  OBJECTIVE
  The objective of the study was to expand this mutational spectrum to better delineate the SLCO2A1 deficiency phenotype and investigate the clinical and metabolic characteristics of a cohort of subjects with PHO.
  
  
  METHODS
  Eleven affected individuals and their available healthy family members from 9 unrelated Chinese families with PHO (7 of which were previously undescribed) were clinically studied. The SLCO2A1 gene was screened and analyzed. Urinary levels of prostaglandin E₂ (PGE₂) and prostaglandin E metabolite (PGE-M) were measured using competitive ELISAs. The serum levels of total T, estradiol, sex hormone-binding protein, LH, FSH, and fasting gastrin were detected.
  
  
  RESULTS
  Nine different SLCO2A1 mutations were identified in affected individuals in the 7 previously undescribed families, 7 of which (Glu165X, Ala286GlnfsX35, Gln356AlafsX77, Gly369Asp, Gly379Glu, Glu465Lys, and c.861+2T>C) were novel. The urinary levels of PGE₂ and PGE-M were much higher in the SLCO2A1-deficient individuals and decreased with age. There was no relationship between sex hormones and PGE₂ or PGE-M. There was no significant difference in the levels of fasting serum gastrin between PHO patients with watery diarrhea and their relatives.
  
  
  CONCLUSIONS
  The present findings broaden the allelic spectrum of SLCO2A1 mutations. The urinary levels of PGE₂ and PGE-M in the SLCO2A1-deficient individuals decreased with age. The measurement of the excreted PGE₂ and PGE-M may have implications in the differential diagnosis, treatment, and follow-up of PHO.
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, People's Republic of China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jin-Wei
authors.initials: JW
authors.lastname: He
authors.forename: Wen-Zhen
authors.initials: WZ
authors.lastname: Fu
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Zhang
authors.forename: Zhen-Lin
authors.initials: ZL
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000595:Amino Acid Sequence; D002681:China; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D015232:Dinoprostone / Q000652:urine; D005192:Family Health; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D027361:Organic Anion Transporters / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010004:Osteoarthropathy, Primary Hypertrophic / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology / Q000652:urine; D010375:Pedigree; D011453:Prostaglandins / Q000652:urine; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D055815:Young Adult
chemical_list: D027361:Organic Anion Transporters; D011453:Prostaglandins; C503526:SLCO2A1 protein, human; C060526:7-hydroxy-5,11-dioxotetranorprostane-1,16-dioic acid; D015232:Dinoprostone