Endocrine Abstracts

Introduction: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant condition characterized by varying combinations of endocrine tumors and commonly accompanying hyperplasia within the parathyroid gland, anterior pituitary and gastrointestinal tract. Heterozygous germline mutation of the tumor suppressor gene MEN1 is the most common cause of the disease. Molecular genetic testing of menin gene, in which mutation is known to cause MEN1 syndrome, detects pathogenic variants in approximately 80%-90% of probands with familial background and in approximately 65% of sporadically occurring cases.

Aims: Identification and characterization of pathogenic mutations in 2 separate families presenting symptoms of MEN1.

Methods: Detailed family history of both pedigrees was investigated and followed up. In Family 1, pituitary tumor, parathyroid gland adenoma and neuroendocrine tumor appeared. The Family 2 presented with parathyroid gland adenoma. Genomic DNA was extracted by conventional methods from peripheral leukocytes. The entire coding sequence, together with the intron-flanking sequences of the MEN1 gene was analyzed.

Results: In both families, novel pathogenic mutations were identified. The Family 1 is affected by the missense mutation leading to single AA substitution V>E at position 220. In the Family 2, a novel splice site mutation c.30G>T was revealed. Both mutations and locations were searched in the literature and genomic databases but so far no such abnormalities were reported.

Conclusions: Patients who present solid components of potential MEN1 syndrome should be routinely screened for genetic abnormalities. There is limited understanding of tumor biology, behavior, and heterogeneous clinical presentation in MEN1. Abundance of genetic alterations in menin as well as lack of mutational hot spots, prompt the usage of wider genetic analysis including other genes. This work also indicate the necessity of thorough analysis of synonymous alterations as potentially pathogenic splice site mutations.