title: Endocrine profile and phenotype-(epi)genotype correlation in Spanish patients with pseudohypoparathyroidism.
abstract: BACKGROUND
  Recent advances in genetics and epigenetics have revealed an overlap between molecular and clinical features of pseudohypoparathyroidism (PHP) subtypes, broadening the previous spectrum of PHP genotype-phenotype correlations and indicating limitations of the current classification of the disease.
  
  
  OBJECTIVE
  The aim of the study was to screen patients with clinical diagnoses of PHP type I or pseudo-PHP for underlying molecular defects and explore possible correlations between molecular findings and clinical features.
  
  
  METHODS
  We investigated the GNAS locus at the molecular level in 72 affected patients (46 women and 26 men) from 56 nonrelated families. Clinical data were obtained for 63 of these patients (38 women and 25 men).
  
  
  RESULTS
  The molecular analysis showed that 35 patients carried structural mutations, 32 had loss of methylation, and 2 had a 2q37 deletion but did not reveal any (epi)mutation for 3 patients. Comparing these results and the clinical data, we observed that a younger age at diagnosis was associated with structural defects at the GNAS gene and epigenetic defects with a diagnosis later in life (9.19 ± 1.64 vs 24.57 ± 2.28 years, P < .0001).
  
  
  CONCLUSIONS
  This first global review of PHP in Spain highlights the importance of a detailed clinical and genetic study of each patient and the integrated analysis of the findings from the two approaches. It may also help geneticists and clinicians to raise the suspicion of PHP earlier, reach more accurate diagnoses, and provide patients with PHP and their families with useful genetic information and counseling, thereby improving outcomes and quality of life.
authors.affiliation: Endocrinology and Diabetes Research Group, Hospital Universitario de Cruces, Universidad del País Vasco-Euskal Herriko Unibertsitatea, 48903 Barakaldo, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernández-Rebollo
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lecumberri
authors.forename: Sonia
authors.initials: S
authors.lastname: Gaztambide
authors.forename: Lorea
authors.initials: L
authors.lastname: Martinez-Indart
authors.forename: Guiomar
authors.initials: G
authors.lastname: Perez de Nanclares
authors.forename: Luis
authors.initials: L
authors.lastname: Castaño
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D002864:Chromogranins; D002872:Chromosome Deletion; D019175:DNA Methylation; D004700:Endocrine System Diseases / Q000209:etiology*; D044127:Epigenesis, Genetic; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics* / Q000378:metabolism; D056726:Genetic Association Studies; D006801:Humans; D006996:Hypocalcemia / Q000209:etiology; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011547:Pseudohypoparathyroidism / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D011556:Pseudopseudohypoparathyroidism / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D012720:Severity of Illness Index; D013030:Spain; D055815:Young Adult
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs