title: Pseudohypoparathyroidism type 1b due to paternal uniparental disomy of chromosome 20q.
abstract: BACKGROUND
  Pseudohypoparathyroidism type 1b (PHP1b) is the result of end-organ resistance to PTH and other hormones such as TSH in the absence of any features of Albright's hereditary osteodystrophy. Patients with PHP1b show imprinting abnormalities at the complex GNAS locus. The molecular cause of autosomal dominant familial PHP1b has been well-defined with identification of microdeletions within the GNAS locus or the nearby STX16, but the molecular mechanism of the GNAS imprinting defects in sporadic PHP1b cases remains elusive.
  
  
  OBJECTIVE
  We investigated the underlying molecular mechanism of GNAS imprinting defects in two patients with sporadic PHP1b.
  
  
  RESULTS
  We identified paternal uniparental disomy of the long arm of chromosome 20 (patUPD20) in two unrelated patients with sporadic PHP1b. This provides an explanation for the patients' GNAS methylation abnormalities and hormone resistance. Our data and a review of the six published cases of patUPD20 suggest that high birth weight and/or early-onset obesity and macrocephaly may also represent features of patUPD20.
  
  
  CONCLUSIONS
  We suggest that patUPD20 should be considered in the evaluation of patients with sporadic PHP1b.
authors.affiliation: Department of Clinical Genetics, Nottingham University Hospitals National Health Service Trust, Nottingham NG5 1PB, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Dixit
authors.forename: K E
authors.initials: KE
authors.lastname: Chandler
authors.forename: M
authors.initials: M
authors.lastname: Lever
authors.forename: R L
authors.initials: RL
authors.lastname: Poole
authors.forename: H
authors.initials: H
authors.lastname: Bullman
authors.forename: M Z
authors.initials: MZ
authors.lastname: Mughal
authors.forename: M
authors.initials: M
authors.lastname: Steggall
authors.forename: M
authors.initials: M
authors.lastname: Suri
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002864:Chromogranins; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D005220:Fathers; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D006801:Humans; D008297:Male; D011547:Pseudohypoparathyroidism / Q000175:diagnosis / Q000235:genetics*; D012189:Retrospective Studies; D024182:Uniparental Disomy / Q000175:diagnosis / Q000235:genetics*
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs