title: GNAS mutation detection is related to disease severity in girls with McCune-Albright syndrome and precocious puberty.
abstract: BACKGROUND
  McCune-Albright syndrome (MAS) is characterized by a triad of gonadotropin-independent precocious puberty, café au lait skin pigmentation and fibrous dysplasia of bone. MAS is due to activating mutations of GNAS, the gene encoding Gsalpha. Interest exists in the use of GNAS mutation analysis to make a definitive diagnosis when the phenotype is not diagnostic, i.e. in partial forms of MAS. The utility of using peripheral blood for mutation analysis in this setting has not been thoroughly evaluated.
  
  
  OBJECTIVE
  We performed a systematic analysis of genomic DNA for the detection of GNAS activating mutations in girls with MAS who presented with precocious puberty to evaluate whether identification of an activating mutation in peripheral blood is related to the presence of other features of MAS.
  
  
  METHODS
  Genomic DNA was isolated from blood from 13 girls with gonadotropin-independent precocious puberty. A polymerase chain reaction (PCR)-based technique was performed for GNAS mutation identification.
  
  
  RESULTS
  GNAS activating mutations were identified in 4 patients, all of whom had classic MAS based on clinical evidence.
  
  
  CONCLUSIONS
  Detection of activating mutations in leukocyte genomic DNA extracted from peripheral blood samples from girls with gonadotropin-independent precocious puberty was associated with the presence of other phenotypic manifestations of MAS. Until improvements in the diagnostic utility of GNAS activating mutation analysis from leukocyte genomic DNA occur, such testing in patients with atypical forms of MAS should continue to be reserved for research settings.
authors.affiliation: Department of Pediatrics, Division of Endocrinology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh PA 15213-2524, USA.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Wagoner
authors.forename: Rosemary
authors.initials: R
authors.lastname: Steinmetz
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Bethin
authors.forename: Erica A
authors.initials: EA
authors.lastname: Eugster
authors.forename: Ora H
authors.initials: OH
authors.lastname: Pescovitz
authors.forename: Tamara S
authors.initials: TS
authors.lastname: Hannon
mesh_terms: D019080:Cafe-au-Lait Spots / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002864:Chromogranins; D005260:Female; D005357:Fibrous Dysplasia of Bone / Q000235:genetics; D005359:Fibrous Dysplasia, Polyostotic / Q000235:genetics*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007962:Leukocytes; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011629:Puberty, Precocious / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs