There is abundant evidence published associating the PRKAR1A gene with Carney complex, type 1, since the gene-disease relationship was first proposed by Kirschner et al. (2000). Multiple case level studies have been performed with CNC patients that have variants in the PRKAR1A gene. Western-blot analysis of primary cell lines from multiple patients indicate that nonsense and frameshift mutations led to NMD. prkar1a +/− mice exhibited extracardiac tumorigenesis, developed sarcomas and hepatocellular carcinomas as well as thyroid, adrenocortical and mesenchymal tumors, which sharing similar phenotypes to CNC patients. In patient cells from three families, both the stimulation of kinase activity with cAMP and the inhibition of that stimulation by PKI were greater in CNC tumours than in those in the control samples. All of these types of evidence are consistent with a definitive relationship between the PRKAR1A gene and Carney complex, type 1.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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