Metabolic expressivity of human genetic variants: NMR metabotyping of MEN1 pathogenic mutants.

Functional consequences of mutations in predisposition genes for familial cancer syndromes remain often elusive, especially when the corresponding gene products play pleiotropic functions and interact with numerous partners. Understanding the consequences of these genetic alterations requires access to their functional effects at the phenotypic level. Nuclear magnetic resonance (NMR) has emerged as a promising functional genomics probe, through its ability to monitor the consequences of genetic variations at the biochemical level.

MEN1 missense mutations impair sensitization to apoptosis induced by wild-type menin in endocrine pancreatic tumor cells.

Background & Aims: Missense mutations account for 30% of mutations identified in patients with the multiple endocrine neoplasia type 1 (MEN1) syndrome. They raise several issues: the distinction between pathogenic mutations and polymorphisms is sometimes difficult and the functional effects of missense mutations are unclear. We aimed to evaluate the functional consequences of missense MEN1 mutations in an appropriate endocrine cellular context.