Vladimir Vasilev1, Adrian F Daly, Albert Thiry, Patrick Petrossians, Frederic Fina, Liliya Rostomyan, Monique Silvy, Alain Enjalbert, Anne Barlier, Albert Beckers. 1. 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.
Abstract
CONTEXT: 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. DESIGN: This was a comprehensive autopsy and genetic analysis. SETTING: The study was conducted at a tertiary referral university hospital. PATIENTS: An adult male patient with MAS and severe disease burden including gigantism was the subject of the study. INTERVENTION(S): 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. MAIN OUTCOME MEASURE: 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.
CONTEXT: 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. DESIGN: This was a comprehensive autopsy and genetic analysis. SETTING: The study was conducted at a tertiary referral university hospital. PATIENTS: An adult male patient with MAS and severe disease burden including gigantism was the subject of the study. INTERVENTION(S): 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. MAIN OUTCOME MEASURE: 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.R201CGNAS1 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: Adrian F Daly; Bo Yuan; Frederic Fina; Jean-Hubert Caberg; Giampaolo Trivellin; Liliya Rostomyan; Wouter W de Herder; Luciana A Naves; Daniel Metzger; Thomas Cuny; Wolfgang Rabl; Nalini Shah; Marie-Lise Jaffrain-Rea; Maria Chiara Zatelli; Fabio R Faucz; Emilie Castermans; Isabelle Nanni-Metellus; Maya Lodish; Ammar Muhammad; Leonor Palmeira; Iulia Potorac; Giovanna Mantovani; Sebastian J Neggers; Marc Klein; Anne Barlier; Pengfei Liu; L'Houcine Ouafik; Vincent Bours; James R Lupski; Constantine A Stratakis; Albert Beckers Journal: Endocr Relat Cancer Date: 2016-03-02 Impact factor: 5.678
Authors: Junhua Zhou; Elena A B Azizan; Claudia P Cabrera; Fabio L Fernandes-Rosa; Sheerazed Boulkroun; Giulia Argentesi; Emily Cottrell; Laurence Amar; Xilin Wu; Sam O'Toole; Emily Goodchild; Alison Marker; Russell Senanayake; Sumedha Garg; Tobias Åkerström; Samuel Backman; Suzanne Jordan; Satyamaanasa Polubothu; Daniel M Berney; Anna Gluck; Kate E Lines; Rajesh V Thakker; Antoinette Tuthill; Caroline Joyce; Juan Pablo Kaski; Fiona E Karet Frankl; Lou A Metherell; Ada E D Teo; Mark Gurnell; Laila Parvanta; William M Drake; Eva Wozniak; David Klinzing; Jyn Ling Kuan; Zenia Tiang; Celso E Gomez Sanchez; Per Hellman; Roger S Y Foo; Charles A Mein; Veronica A Kinsler; Peyman Björklund; Helen L Storr; Maria-Christina Zennaro; Morris J Brown Journal: Nat Genet Date: 2021-08-12 Impact factor: 41.307
Authors: Mustafa Tosur; Michael T Collins; Stephen W Ponder; Constantine A Stratakis; Lefkothea P Karaviti; George S Jeha Journal: Glob Pediatr Health Date: 2017-11-21