Session: SAT 41-52-HPA Axis & Disease States
Poster Board SAT-47
In this study we report large PRKAR1A gene deletions in 7 CNC patients. The deletions were identified by microarray-based Comparative Genomic Hybridization (array-CGH) and confirmed by Sanger sequencing of the boundaries and, in one case of complete deletion of the PRKAR1A gene - through Fluorescent in situ Hybridization (FISH). Quantitative PCR showed that these deletions lead to decreased PRKAR1A mRNA levels. Thus, we show that deletions of PRKAR1A cause CNC through haploinsufficiency, which is the molecular mechanism of the disease in the vast majority of the PRKAR1A point mutation carriers.
These deletions spread through all functional R1a domains and with significantly decreased PRKAR1A expression compared to normal. Interestingly preliminary clinical data indicated that these patients with extended PRKAR1A deletions also shared a different phenotype.
Until now only several cases of CNC patients with large PRKAR1A deletions have been described. In this study we present new cases that extend PRKAR1A mutational spectrum. Our data suggest that testing for large PRKAR1A alterations might need to be considered for routine genetic diagnosis of CNC.
Nothing to Disclose: PS, ADH, EL, AV, AM, EG, MK, AF, OZ, CAS
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