, Volume 15, Issue 1, pp 129–135 | Cite as

Identification of a novel mutation of the PRKAR1A gene in a patient with Carney complex with significant osteoporosis and recurrent fractures

  • Labrini PapanastasiouEmail author
  • Stelios Fountoulakis
  • Nikos Voulgaris
  • Theodora Kounadi
  • Theodosia Choreftaki
  • Akrivi Kostopoulou
  • George Zografos
  • Charalampos Lyssikatos
  • Constantine A. Stratakis
  • George Piaditis
Case report


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. DESIGN: Clinical case report. CASE REPORT: 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)]. CONCLUSION: 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.

Key words

Carney complex Hypercortisolism Osteoporosis PRKAR1A gene PPNAD 


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Copyright information

© Hellenic Endocrine Society 2016

Authors and Affiliations

  • Labrini Papanastasiou
    • 1
    Email author
  • Stelios Fountoulakis
    • 1
  • Nikos Voulgaris
    • 1
  • Theodora Kounadi
    • 1
  • Theodosia Choreftaki
    • 2
  • Akrivi Kostopoulou
    • 2
  • George Zografos
    • 3
  • Charalampos Lyssikatos
    • 4
  • Constantine A. Stratakis
    • 4
  • George Piaditis
    • 1
  1. 1.Department of Endocrinology and Diabetes CenterGeneral Hospital “G. Gennimatas”AthensGreece
  2. 2.Department of Pathology“G. Gennimatas” General HospitalAthensGreece
  3. 3.Department of Surgery“G. Gennimatas” General HospitalAthensGreece
  4. 4.Section on Endocrinology & Genetics, Program on Developmental Endocrinology & GeneticsNational Institute of Child Health and Human Development, National Institutes of HealthBethesdaUSA

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