title: Clinical characterization and molecular classification of 12 Korean patients with pseudohypoparathyroidism and pseudopseudohypoparathyroidism.
abstract: BACKGROUND
  Pseudohypoparathyroidism (PHP) is defined as resistance toward parathyroid hormones. PHP and pseudopseudohypoparathyroidism (PPHP) are rare disorders resulting from genetic and epigenetic aberrations within or upstream of the GNAS locus. This study investigated the clinical characteristics and performed a molecular analysis of PHP and PPHP.
  
  
  METHODS
  A total of 12 patients with (P)PHP from 11 unrelated families (4 with PHP-Ia, 6 with PHP-Ib, and 2 with PPHP) were characterized using both clinical and molecular methods. Clinical features included the presenting symptoms, Albright hereditary osteodystrophy features, and resistance to hormones. Comprehensive analysis of the GNAS and STX16 loci was undertaken to investigate the molecular defects underlying (P)PHP.
  
  
  RESULTS
  All PHP-Ib patients displayed hypocalcemic symptoms. All PHP-Ia patients showed resistance toward TSH, in addition to PTH. In most patients with PHP, when the diagnosis of PHP was first established, hypocalcemia and hyperphosphatemia were associated with a significant increase in serum PTH levels. One patient with PHP-Ia was diagnosed with growth hormone deficiency and showed a good response to human recombinant growth hormone therapy. 6 patients with PHP-Ia and PPHP showed 5 different mutations in the GNAS gene. 5 patients with PHP-Ib displayed a loss of differentially methylated region (DMR) imprints of the maternal GNAS. One PHP-Ib patient showed a de novo microdeletion in STX16 and a loss of methylation of exon A/B on the maternal allele. No patients revealed paternal disomy among 4 patients with PHP-Ib.
  
  
  CONCLUSIONS
  Identification of the molecular causes of PHP and PPHP explains their distinctive clinical features and enables confirmation of the diagnosis and exact genetic counseling.
authors.affiliation: Department of Pediatrics, Hanyang University Guri Hopistal, Hanyang University College of Medicine, Guri, Republic of Korea.
authors.forename: S Y
authors.initials: SY
authors.lastname: Cho
authors.forename: Y A
authors.initials: YA
authors.lastname: Yoon
authors.forename: C-S
authors.initials: CS
authors.lastname: Ki
authors.forename: H J
authors.initials: HJ
authors.lastname: Huh
authors.forename: H-W
authors.initials: HW
authors.lastname: Yoo
authors.forename: B H
authors.initials: BH
authors.lastname: Lee
authors.forename: G-H
authors.initials: GH
authors.lastname: Kim
authors.forename: J-H
authors.initials: JH
authors.lastname: Yoo
authors.forename: S-Y
authors.initials: SY
authors.lastname: Kim
authors.forename: S J
authors.initials: SJ
authors.lastname: Kim
authors.forename: Y B
authors.initials: YB
authors.lastname: Sohn
authors.forename: S W
authors.initials: SW
authors.lastname: Park
authors.forename: R
authors.initials: R
authors.lastname: Huh
authors.forename: M S
authors.initials: MS
authors.lastname: Chang
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: Y
authors.initials: Y
authors.lastname: Kwun
authors.forename: S H
authors.initials: SH
authors.lastname: Maeng
authors.forename: D-K
authors.initials: DK
authors.lastname: Jin
mesh_terms: D000328:Adult; D000375:Aging; D044466:Asian People; D002648:Child; D002675:Child, Preschool; D002864:Chromogranins; D004247:DNA / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D017353:Gene Deletion; D006128:Growth; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction; D011547:Pseudohypoparathyroidism / Q000097:blood* / Q000235:genetics*; D011556:Pseudopseudohypoparathyroidism / Q000097:blood* / Q000235:genetics*; D051438:Syntaxin 16 / Q000235:genetics
chemical_list: D002864:Chromogranins; C496118:STX16 protein, human; D051438:Syntaxin 16; D004247:DNA; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs