title: Identification of novel genetic variants in phosphodiesterase 8B (PDE8B), a cAMP-specific phosphodiesterase highly expressed in the adrenal cortex, in a cohort of patients with adrenal tumours.
abstract: BACKGROUND
  Genetic aberrations in various components of cAMP signalling pathway predispose to endocrine tumours. Mutations in the phosphodiesterases (PDEs) are involved in the predisposition to adrenocortical neoplastic conditions.
  
  
  OBJECTIVE
  To screen for genetic variations in PDE8B among patients with different types of adrenocortical tumours.
  
  
  METHODS
  This is a case-control study followed by functional analyses. Two hundred and sixteen unrelated patients with different types of adrenocortical tumours and 192 healthy control individuals participated in the study.
  
  
  METHODS
  Bidirectional Sanger sequencing, in vitro cell line transfection and in silico modelling are used in this study.
  
  
  RESULTS
  Nine different PDE8B sequence changes, six novel and three previously reported, were identified in our patients and controls. Two of the variations, seen only in the patient group, showed significant potential to impair protein function, both in vitro and in silico.
  
  
  CONCLUSIONS
  PDE8B is another PDE gene in which variations may contribute to predisposition of adrenocortical tumours.
authors.affiliation: Section on Endocrinology and Genetics and Pediatric Endocrinology Training Program, both at Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1103, USA.
authors.forename: Anya
authors.initials: A
authors.lastname: Rothenbuhler
authors.forename: Anelia
authors.initials: A
authors.lastname: Horvath
authors.forename: Rossella
authors.initials: R
authors.lastname: Libé
authors.forename: Fabio R
authors.initials: FR
authors.lastname: Faucz
authors.forename: Amato
authors.initials: A
authors.lastname: Fratticci
authors.forename: Marie L
authors.initials: ML
authors.lastname: Raffin Sanson
authors.forename: Delphine
authors.initials: D
authors.lastname: Vezzosi
authors.forename: Monalisa
authors.initials: M
authors.lastname: Azevedo
authors.forename: Isaak
authors.initials: I
authors.lastname: Levy
authors.forename: Madson Q
authors.initials: MQ
authors.lastname: Almeida
authors.forename: Maya
authors.initials: M
authors.lastname: Lodish
authors.forename: Maria
authors.initials: M
authors.lastname: Nesterova
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bertherat
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics*; D000302:Adrenal Cortex / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015105:3',5'-Cyclic-AMP Phosphodiesterases; C468781:PDE8B protein, human