title: McCune Albright syndrome and bilateral adrenal hyperplasia: the GNAS mutation may only be present in adrenal tissue.
abstract: OBJECTIVE
  Corticotropin (ACTH)-independent hypercortisolism due to bilateral adrenocortical hyperplasia (BAH) in infancy is an extremely rare condition that is often caused by McCune Albright syndrome (MAS). MAS is caused by an activating mutation of the GNAS gene which leads to increased cyclic (c) adenosine monophosphate (AMP) signaling. Most forms of BAH are linked to increased cAMP signaling. We report the case of an infant with MAS who had BAH.
  
  
  METHODS
  Genomic DNA fragments from blood and adrenal tissue encompassing regions (exons 8 and 9) with the hot spot activating missense GNAS mutations were amplified by classical bidirectional Sanger sequencing.
  
  
  RESULTS
  The infant was found to carry the most common GNAS mutation, in exon 8 (c.602G >A, p. R201H), only in her adrenocortical tissue, despite extensive skin and other findings.
  
  
  CONCLUSIONS
  We conclude that infants with MAS, despite absence of the GNAS activating mutation in blood, may still have significant clinical findings, including ACTH-independent hypercortisolism. Molecular confirmation of the diagnosis should be sought at the tissue level in these patients.
authors.affiliation: Section on Endocrinology & Genetics, Program on Developmental Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Angelousi
authors.affiliation: Department of Pediatrics, University Hospital Motol, Prague, Czech Republic.
authors.forename: Filip
authors.initials: F
authors.lastname: Fencl
authors.affiliation: Section on Endocrinology & Genetics, Program on Developmental Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, USA.
authors.forename: Fabio R
authors.initials: FR
authors.lastname: Faucz
authors.affiliation: Department of Pediatrics, University Hospital Motol, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Malikova
authors.affiliation: Department of Pediatrics, University Hospital Motol, Prague, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Sumnik
authors.affiliation: Department of Pediatrics, University Hospital Motol, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Lebl
authors.affiliation: Section on Endocrinology & Genetics, Program on Developmental Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, USA.
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D002864:Chromogranins; D005260:Female; D005359:Fibrous Dysplasia, Polyostotic / Q000235:genetics*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D007223:Infant
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs