Analysis of MEN1 c.482G>A (p.Gly161Asp) mutation in a pedigree with familial multiple endocrine neoplasia type 1

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the development of neuroendocrine tumors, which in turn are caused by mutations in the MEN1 gene. In the present study, a case of a 46-year-old woman who was clinically diagnosed with MEN1 based on the presence of prolactinoma and bilateral parathyroid adenoma was reported. The patient's serum prolactin (PRL) levels were successfully controlled via bromocriptine therapy, and the serum levels of calcium and intact parathyroid hormone (PTH) reduced one day following parathyroidectomy. Genetic testing revealed a missense mutation c.482G>A (p.Gly161Asp) in exon 3 of the MEN1 gene, and it led to the identification of two carriers in the pedigree (patient's elder sister and brother). Both of the carriers revealed to have high blood calcium, PTH and PRL. The mutation identified in this pedigree has never been reported in China. The sequence alignments and tertiary structure of menin protein were made by Polyphen2, SNPs3D, and SIFT, which were used to predict the function of mutant menin. Since the mutant menin may interfere with the menin-JunD or menin-Smad3 interactions, further investigations are necessary to explore the function of mutant protein. In view of that, identification of mutations and longtime follow-up are important for patients with a pedigree clearly indicating MEN1.