title: New mechanisms involved in paternal 20q disomy associated with pseudohypoparathyroidism.
abstract: OBJECTIVE
  Type I pseudohypoparathyroidism (PHP-I) can be subclassified into Ia and Ib, depending on the presence or absence of Albright's hereditary osteodystrophy's phenotype, diminished α-subunit of the stimulatory G protein (G(s)α) activity and multihormonal resistance. Whereas PHP-Ia is mainly associated with heterozygous inactivating mutations in G(s)α-coding exons of GNAS, PHP-Ib is caused by imprinting defects of GNAS. To date, just one patient with PHP and complete paternal uniparental disomy (UPD) has been described. We sought to identify the underlining molecular defect in twenty patients with parathyroid hormone resistance, hypocalcemia and hyperphosphatemia, and abnormal methylation pattern at GNAS locus.
  
  
  METHODS
  Microsatellite typing and comparative genome hybridization were performed for proband and parents.
  
  
  RESULTS
  We describe four patients with partial paternal UPD of chromosome 20 involving pat20qUPD in one case, from 20q13.13-qter in two cases, and pat20p heterodisomy plus interstitial 20q isodisomy in one patient.
  
  
  CONCLUSIONS
  These observations demonstrate that mitotic recombination of chromosome 20 can also give rise to UPD and PHP, a situation similar to other imprinting disorders, such as Beckwith-Wiedemann syndrome or neonatal diabetes.
authors.affiliation: Endocrinology and Diabetes Research Group, Molecular Genetics Laboratory, Hospital de Cruces, 48903 Barakaldo, Bizkaia, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernández-Rebollo
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lecumberri
authors.forename: Intza
authors.initials: I
authors.lastname: Garin
authors.forename: Javier
authors.initials: J
authors.lastname: Arroyo
authors.forename: Ana
authors.initials: A
authors.lastname: Bernal-Chico
authors.forename: Fernando
authors.initials: F
authors.lastname: Goñi
authors.forename: Rosa
authors.initials: R
authors.lastname: Orduña
authors.forename: Luis
authors.initials: L
authors.lastname: Castaño
authors.forename: Guiomar Pérez
authors.initials: GP
authors.lastname: de Nanclares
mesh_terms: D000328:Adult; D002675:Child, Preschool; D002864:Chromogranins; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D008297:Male; D008745:Methylation; D018895:Microsatellite Repeats; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011547:Pseudohypoparathyroidism / Q000235:genetics*; D024182:Uniparental Disomy
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs