title: [Absence of PRKAR1A loss of heterozygosity in laser-captured microdissected pigmented nodular adrenocortical tissue from a patient with Carney complex caused by the novel nonsense mutation p.Y21X].
abstract: OBJECTIVE
  Primary pigmented nodular adrenocortical disease (PPNAD) is the main endocrine manifestation of Carney complex, a multiple neoplasia syndrome caused by PRKAR1A gene mutations. The presence of PRKAR1A loss of heterozygosity (LOH) in adrenocortical tumorigenesis remains controversial. The aim of the present study is to investigate the presence of PRKAR1A LOH in adrenocortical cells in a patient with Carney complex.
  
  
  METHODS
  The LOH was investigated using a PRKAR1A informative intragenic marker by GeneScan software analysis in DNA obtained from laser-captured microdissected cells of several adrenal nodules.
  
  
  METHODS
  A young adult male patient with Carney complex and his family were studied.
  
  
  RESULTS
  A novel heterozygous mutation (p. Y21X) was identified at PRKAR1A in blood DNA of the male proband and his relatives. No PRKAR1A LOH was evidenced in the laser-captured microdissected cells from PPNAD tissue by different methodologies.
  
  
  CONCLUSIONS
  We identified a new PRKAR1A nonsense mutation and in addition we did not evidence PRKAR1A LOH in laser-captured nodules cells, suggesting that adrenocortical tumorigenesis in PPNAD may occurs apart from the second hit.
authors.affiliation: Hospital das Clínicas, Universidade de São Paulo, SP, Brasil.
authors.forename: Madson Q
authors.initials: MQ
authors.lastname: Almeida
authors.forename: Luciana Pinto
authors.initials: LP
authors.lastname: Brito
authors.forename: Sorahia
authors.initials: S
authors.lastname: Domenice
authors.forename: Marcia Helena Soares
authors.initials: MH
authors.lastname: Costa
authors.forename: Emilia Modolo
authors.initials: EM
authors.lastname: Pinto
authors.forename: Cynthia A Toledo
authors.initials: CA
authors.lastname: Osório
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Latronico
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Maria Candida B V
authors.initials: MC
authors.lastname: Fragoso
mesh_terms: D000293:Adolescent; D000302:Adrenal Cortex / Q000166:cytology / Q000473:pathology*; D018389:Codon, Nonsense / Q000097:blood / Q000235:genetics*; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics*; D005260:Female; D006801:Humans; D007834:Lasers; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009377:Multiple Endocrine Neoplasia / Q000235:genetics*; D010375:Pedigree
chemical_list: D018389:Codon, Nonsense; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human