A novel menin gene deletional mutation in a little series of Italian patients affected by apparently sporadic multiple endocrine neoplasia type 1 syndrome

• Published in: Journal of endocrinological investigation 2012-02, Vol.35 (2), p.124-128
• Main Authors: Giacché, M., Panarotto, A., Mori, L., Daffini, L., Tacchetti, M. C., Pirola, I., Agabiti Rosei, E., Castellano, M.
• Format: Article
• Language: English
• Subjects: Adenoma - etiology; Adenoma - genetics; Adult; Cohort Studies; DNA Mutational Analysis; Endocrinology; Female; Humans; Insulinoma - etiology; Insulinoma - genetics; Italy; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Multiple Endocrine Neoplasia Type 1 - complications; Multiple Endocrine Neoplasia Type 1 - genetics; Pancreatic Neoplasms - etiology; Pancreatic Neoplasms - genetics; Parathyroid Neoplasms - etiology; Parathyroid Neoplasms - genetics; Proto-Oncogene Proteins - genetics; Rapid Communication; Sequence Deletion - physiology; Syndrome
• ISSN: 0391-4097; 1720-8386
• DOI: 10.1007/BF03345419

Aim: To perform a genetic screening for the multiple endocrine neoplasia type 1 ( MEN1 ) gene mutations in patients affected by an apparently sporadic form of the disease, referred to an internal medicine unit of a large general hospital. Subjects and methods: In a group of 12 consecutive patients presenting clinical features of MEN type 1 syndrome, we performed a genetic screening for germline MEN1 gene mutations, including complete sequencing of the coding region (exons 2 to 10) and multiplex ligation-dependent probe amplification analysis for large deletion detection. Results: Among these patients affected by apparently sporadic MEN type 1 syndrome, a targeted clinical history could detect indirect support for a diagnosis of familial condition only in 2 cases. The genetic screening identified pathogenic germline MEN1 gene mutations in 3 patients (25%). A previously unknown 18 base-pair deletion within exon 3, c.564_581 delCAATGGGGAGCAGACAGC, resulting in loss of 6 amino acids (pAsp189_Ala194del), was found in heterozygosis in a woman affected by primary hyperparathyroidism and multifocal pancreatic neoplasia. Conclusions: Our results underscore the importance of performing genetic testing also in apparently sporadic MEN1 patients and extend the list of molecular variants leading to inactivation of the MEN1 gene.