title: Identification of a novel mutation of the PRKAR1A gene in a patient with Carney complex with significant osteoporosis and recurrent fractures.
abstract: OBJECTIVE
  Carney complex (CNC) is a rare autosomal dominant multiple neoplasia syndrome characterized by the presence of endocrine and non-endocrine tumors. More than 125 different germline mutations of the protein Kinase A type 1-α regulatory subunit (PRKAR1A) gene have been reported. We present a novel PRKAR1A gene germline mutation in a patient with severe osteoporosis and recurrent vertebral fractures.
  
  
  METHODS
  Clinical case report.
  
  
  METHODS
  A 53-year-old male with a medical history of surgically removed recurrent cardiac myxomas was evaluated for repeated low-pressure vertebral fractures and severe osteoporosis. Physical examination revealed spotty skin pigmentation of the lower extremities and papules in the nuchal and thoracic region. The presence of hypercortisolism due to micronodular adrenal disease and the history of cardiac myxomas suggested the diagnosis of CNC; the patient underwent detailed imaging investigation and genetic testing.
  
  
  METHODS
  Standard imaging and clinical testing; DNA was sequenced by the Sanger method.
  
  
  RESULTS
  Sequence analysis from peripheral lymphocytes DNA revealed a novel heterozygous point mutation at codon 172 of exon 2 (c.172G>T) of the PRKAR1A gene, resulting in early termination of the PRKAR1A transcript [p.Glu58Ter (E58X)].
  
  
  CONCLUSIONS
  We report a novel point mutation of the PRKAR1A gene in a patient with CNC who presented with significant osteoporosis and fractures. Low bone mineral density along with recurrent myxomas should point to the diagnosis of CNC.
authors.affiliation: Department of Endocrinology and Diabetes Center, "G. Gennimatas" General Hospital, Athens, Greece.
authors.forename: Labrini
authors.initials: L
authors.lastname: Papanastasiou
authors.affiliation: Department of Endocrinology and Diabetes Center, "G. Gennimatas" General Hospital, Athens, Greece.
authors.forename: Stelios
authors.initials: S
authors.lastname: Fountoulakis
authors.affiliation: Department of Endocrinology and Diabetes Center, "G. Gennimatas" General Hospital, Athens, Greece.
authors.forename: Nikos
authors.initials: N
authors.lastname: Voulgaris
authors.affiliation: Department of Endocrinology and Diabetes Center, "G. Gennimatas" General Hospital, Athens, Greece.
authors.forename: Theodora
authors.initials: T
authors.lastname: Kounadi
authors.affiliation: Department of Pathology, "G. Gennimatas" General Hospital, Athens, Greece.
authors.forename: Theodosia
authors.initials: T
authors.lastname: Choreftaki
authors.affiliation: Department of Pathology, "G. Gennimatas" General Hospital, Athens, Greece.
authors.forename: Akrivi
authors.initials: A
authors.lastname: Kostopoulou
authors.affiliation: Department of Surgery, "G. Gennimatas" General Hospital, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Zografos
authors.affiliation: Section on Endocrinology & Genetics, Program on Developmental Endocrinology & Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, USA.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Lyssikatos
authors.affiliation: Section on Endocrinology & Genetics, Program on Developmental Endocrinology & Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, USA.
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
authors.affiliation: Department of Endocrinology and Diabetes Center, "G. Gennimatas" General Hospital, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Piaditis
mesh_terms: D056733:Carney Complex / Q000235:genetics* / Q000378:metabolism*; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics / Q000378:metabolism*; D005598:Fractures, Spontaneous / Q000209:etiology* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010024:Osteoporosis / Q000209:etiology* / Q000473:pathology
chemical_list: D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human