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MEN4 variant of unknown significance in two generations of patients presenting with Cushing disease
Stephanie Gambino1, Akanksha Aggarwal2, Jerry Vockley3
1Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh/University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Abstract:
Cushing disease is the most common form of endogenous hypercortisolism and can be associated with familial endocrine syndromes, including multiple endocrine neoplasia type 4 (MEN4). We report a case of a father and daughter who both presented with Cushing disease and were found to have the same variant of unknown significance in the CDKN1B gene (c.280 C>T, p.P94S), the gene responsible for MEN4. They were treated surgically and are in remission from Cushing disease. This case raises the possibility that the variant could be pathogenic, despite in silico predictions to the contrary.
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