title: McCune-Albright syndrome: a detailed pathological and genetic analysis of disease effects in an adult patient.
abstract: BACKGROUND
  McCune Albright syndrome (MAS) is a clinical association of endocrine and nonendocrine anomalies caused by postzygotic mutation of the GNAS1 gene, leading to somatic activation of the stimulatory α-subunit of G protein (Gsα). Important advances have been made recently in describing pathological characteristics of many MAS-affected tissues, particularly pituitary, testicular, and adrenal disease. Other rarer disease related features are emerging.
  
  
  OBJECTIVE
  The objective of the investigation was to study the pathological and genetic findings of MAS on a tissue-by-tissue basis in classically and nonclassically affected tissues.
  
  
  METHODS
  This was a comprehensive autopsy and genetic analysis.
  
  
  METHODS
  The study was conducted at a tertiary referral university hospital.
  
  
  METHODS
  An adult male patient with MAS and severe disease burden including gigantism was the subject of the study.
  
  
  METHODS
  Interventions included clinical, hormonal, and radiographic studies and gross and microscopic pathology analyses, conventional PCR, and droplet digital PCR analyses of affected and nonaffected tissues.
  
  
  METHODS
  Pathological findings and the presence of GNAS1 mutations were measured.
  
  
  RESULTS
  The patient was diagnosed with MAS syndrome at 6 years of age based on the association of café-au-lait spots and radiological signs of polyostotic fibrous dysplasia. Gigantism developed and hyperprolactinemia, hypogonadotropic hypogonadism, and hyperparathyroidism were diagnosed throughout the adult period. The patient died at the age of 39 years from a pulmonary embolism. A detailed study revealed mosaiscism for the p.R201C GNAS1 mutation distributed across many endocrine and nonendocrine tissues. These genetically implicated tissues included rare or previously undescribed disease associations including primary hyperparathyroidism and hyperplasia of the thymus and endocrine pancreas.
  
  
  CONCLUSIONS
  This comprehensive pathological study of a single patient highlights the complex clinical profile of MAS and illustrates important advances in understanding the characteristics of somatic GNAS1-related pathology across a wide range of affected organs.
authors: Departments of Endocrinology (V.V., A.F.D., P.P., L.R., A.Be.) and Pathological Anatomy (A.T.), Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart Tilman, 4000 Liège, Belgium; Department of Biological Oncology Transfer (F.F.), Laboratory of Medical Biology, Assistance Publique-Hôpitaux de Marseille, 13354 Marseille, France; and Laboratory of Biochemistry and Molecular Biology (M.S., A.E., A.Ba.), Centre Hospitalier Universitaire Conception, University of the Mediterranean, 13007 Marseille, France.
authors: Vladimir
authors: V
authors: Vasilev
authors: Adrian F
authors: AF
authors: Daly
authors: Albert
authors: A
authors: Thiry
authors: Patrick
authors: P
authors: Petrossians
authors: Frederic
authors: F
authors: Fina
authors: Liliya
authors: L
authors: Rostomyan
authors: Monique
authors: M
authors: Silvy
authors: Alain
authors: A
authors: Enjalbert
authors: Anne
authors: A
authors: Barlier
authors: Albert
authors: A
authors: Beckers
mesh_terms: D000328:Adult; D002864:Chromogranins; D017809:Fatal Outcome; D005359:Fibrous Dysplasia, Polyostotic / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D006961:Hyperparathyroidism / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D009030:Mosaicism; D009490:Neurosecretory Systems / Q000473:pathology / Q000502:physiology; D011859:Radiography; D013950:Thymus Gland / Q000473:pathology
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs