Genetics of multiple endocrine neoplasia type 1 syndrome: what's new and what's old

Abstract

Despite its identification in 1997, the functions of the MEN1 gene—the main gene underlying multiple endocrine neoplasia type 1 syndrome—are not yet fully understood. In addition, unlike the RET—MEN2 causative gene—no hot-spot mutational areas or genotype–phenotype correlations have been identified. More than 1,300 MEN1 gene mutations have been reported and are mostly "private” (family specific). Even when mutations are shared at an intra- or inter-familial level, the spectrum of clinical presentation is highly variable, even in identical twins. Despite these inherent limitations for genetic counseling, identifying MEN1 mutations in individual carriers offers them the opportunity to have lifelong clinical surveillance schemes aimed at revealing MEN1-associated tumors and lesions, dictates the timing and scope of surgical procedures, and facilitates specific mutation analysis of relatives to define presymptomatic carriers.