MEN1 family with a novel frameshift mutation

Area of Science:

• Endocrinology
• Genetics
• Oncology

Background:

• Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder predisposing to endocrine and non-endocrine tumors.
• MEN1 syndrome is characterized by variable clinical manifestations due to diverse gene mutations.

Observation:

• A 51-year-old male presented with diarrhea, hypertension, and a history of mesenchymal neoplasia and adrenal adenoma.
• Physical examination revealed lipomas and facial angiofibromas; biochemical tests showed hyperparathyroidism and elevated PRL, chromogranin-A, gastrin, and glucagon.
• Imaging studies were inconclusive for small neuroendocrine tumors, but endoscopic ultrasound identified a pancreatic lesion.

Findings:

• Direct DNA sequencing identified a novel 579delG frameshift mutation in the MEN1 gene in the proband.
• The same mutation was found in three of five offspring, who also exhibited biochemical features of MEN1 syndrome.
• The study identified a novel MEN1 mutation in a family with a seemingly negative history.

Implications:

• This case highlights a novel MEN1 mutation, emphasizing the genetic complexity and variable expressivity of the syndrome.
• Early and specialized investigation is essential for diagnosing MEN1 syndrome, even in the absence of a clear family history.
• The findings underscore the importance of comprehensive genetic and biochemical screening for affected families.