What question did this study set out to answer?

To explore the association of a CDKN1B gene variant with familial Cushing disease.

May 8, 2026Open Access

MEN4 variant of unknown significance in two generations of patients presenting with Cushing disease

Key Points

To explore the association of a CDKN1B gene variant with familial Cushing disease.
Reported case of a father and daughter diagnosed with Cushing disease.
Genetic analysis revealed a shared variant in the CDKN1B gene (c.280 C>T, p.P94S).
Both patients underwent surgical treatment and achieved remission.
Both the father and daughter have the same variant of unknown significance in the CDKN1B gene.
Post-surgery, both patients are in remission from Cushing disease.
The findings suggest the variant may be pathogenic, despite in silico predictions.

Abstract

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 CT, 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.

MEN4 variant of unknown significance in two generations of patients presenting with Cushing disease

Key Points

Abstract

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