作者: Anelia Horvath , Christoforos Giatzakis , Kitman Tsang , Elizabeth Greene , Paulo Osorio
DOI: 10.1038/EJHG.2008.85
关键词:
摘要: Bilateral adrenocortical hyperplasia (BAH) is the second most common cause of corticotropin-independent Cushing syndrome (CS). Genetic forms BAH have been associated with complex syndromes such as Carney Complex and McCune-Albright or may present isolated micronodular disease (iMAD) usually in children young adults CS. A genome-wide association study identified inactivating phosphodiesterase (PDE) 11A (PDE11A)-sequencing defects low-penetrance predisposing factors for iMAD related abnormalities; we also described a mutation (c.914A > C/H305P) cyclic AMP (cAMP)-specific PDE8B, patient iMAD. In this further characterize mutation; found novel PDE8B isoform that highly expressed adrenal gland. This shown to significantly affect ability protein degrade cAMP vitro. Tumor tissues from patients no mutations coding sequence any other genes (PRKAR1A, PDE11A) showed downregulated expression (compared normal cortex). Pde8b detectable gland newborn mice widely mouse tissues. We conclude another PDE gene linked iMAD; it candidate causative lesions signaling pathway possibly tumors