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Large Deletions of the PRKAR1A Gene in Carney Complex

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • P Salpea
  • A Horvath
  • E London
  • A Vetro
  • A Manning
  • E Gourgari
  • M Keil
  • A Forlino
  • O Zuffardi
  • C.A. Stratakis


Background: Carney Complex (CNC) is an autosomal dominant multiple endocrine neoplasia syndrome. PRKAR1A gene encodes for the type 1A regulatory subunit of Protein Kinase A and inactivating mutations have been shown to cause Carney Complex (~70% of CNC patients). Most of these mutations consist of single base substitutions, small indels or combined rearrangements, all of them not exceeding 15bp. Results: In this study we report large deletions at the chromosome 17q24 that include PRKAR1A gene in 11 CNC patients. The deletions were identified by array based Comparative Genomic Hybridization (array-CGH). Quantitative PCR and Western Blot analysis showed that these CNC patients had significantly lower PRKAR1A mRNA and protein levels. Thus, we showed that deletions of the PRKAR1A cause CNC through haploinsufficiency, which is the molecular mechanism of the disease in the vast majority of the PRKAR1A point mutation carriers. Conclusions: These deletions spread to all functional PRKAR1A domains and are associated with significantly decreased PRKAR1A expression compared to control samples. In this study we present new cases that extend the PRKAR1A spectrum. Our data suggest that testing for large PRKAR1A alterations might need to be considered for routine genetic diagnosis of CNC.

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