Endocrine Abstracts

Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant inherited disease with a high degree of penetrance. The three most common locations of tumors are the parathyroid glands, the gastro-duodenum pancreas and/or the anterior pituitary gland. The gene involved in this disease is MEN 1, a tumor suppressor gene located on chromosome 11q13. The objective of our work was to describe the genotype of patients with MEN 1 born in Argentina.

Subjects and Methods

We studied 132 possible carriers of MEN1 born in Argentina: 56 index cases (31 women; mean age 40.42 years (SD 16.2); r: 2–75 years) and 76 asymptomatic first-degree relatives (41 women; age 33.70 (SD 19.1); 2–69 years). The coding region (exons 2–10), the promoter, exon 1 and, the flanking intronic regions of the MEN1 gene were sequenced by the Sanger method. MLPA was used in patients with no mutation findings.

Results

We found mutations throughout the entire gene, in the coding regions, the flanking intronic and splicing sites as reported in the literature. Forty mutations were found in 56 patients (71.4%). The prevalence of mutations was 92% in familial cases and 54.5% in sporadic cases. Of the 31 different pathogenic variants, 11 (38.7%) were reading frame alterations (38.7%) (9 microdeletions, 1 microduplication and 1 microinsertion), 7 (22.6%) were nonsense variants, 7 nonsense (22.6%), 3 mutations in splicing sites (9.7%) and 2 large deletions (6.4%). We found nine novel pathogenic variants.

Conclusions

The genetic diagnosis of this population of 76 with MEN1 allowed us to confirm the diagnosis in 71.4% of the patients and to identify 38% of the first-degree relatives as asymptomatic carriers. Carriers of the mutation may be studied annually according to international guidelines that would improve their survival through early diagnosis of tumors.