We report a family with a novel heterozygous mutation of the menin gene. This gene encodes a tumor suppressor protein which is responsible for multiple endocrine neoplasia type 1. The index female patient presented with symptoms of mild gastric hyperacidity and recurrent kidney stones. Family history revealed, that the daughter, as well as two sisters of the index patient had operations for primary hyperparathyroidism (PHPT). Clinical studies in the index patient showed elevated serum calcium and alkaline phosphatase, low serum phosphate, and increased urinary calcium. Serum parathyroid hormone concentration was increased and osteodensitometry indicated osteoporosis. 99mTc-MIBI scintigraphy revealed isotope accumulation in 3 parathyroid glands. Peptic ulcer was excluded. The patient underwent parathyroidectomy, which resulted in a normalization of serum calcium and parathyroid hormone levels. Two months after surgery the patient developed headache and visual disturbance, and pituitary MRI indicated a large macroadenoma with suprasellar extension measuring 21×15 mm in size. The pituitary adenoma was removed by supraciliar craniotomy and histological examination indicated an FSH/LH-producing adenoma.
Bidirectional sequence analysis of exons 2-10 of the menin gene in peripheral blood of the index patient indicated the presence of two known polymorphisms in exon 3 (R171Q) and in exon 9 (D418D) as well as a novel L301R heterozygous mutation in exon 6. Family screening confirmed the presence of this novel mutation in each of the three relatives affected by PTHP, while the mutation was absent in other family members. We conclude that multiple endocrine neoplasia type 1 in this family was associated with a novel L301R mutation of the menin gene.
01 - 05 Apr 2006
European Society of Endocrinology