Unusual presentation of multiple endocrine neoplasia type 1 in a young woman with a novel mutation of the MEN1 gene

Abstract

We report an unusual presentation of multiple endocrine neoplasia type 1 (MEN 1) in a young woman who was subsequently proven to have a novel mutation of the MEN1 gene. The young patient, aged 25 years, was investigated for abdominal discomfort and left upper abdominal pain. Her family history was unremarkable, except an unknown disorder of her father causing early death. Abdominal ultrasonography (USG) and computed tomography revealed a giant pancreatic tumor measuring 10 cm in diameter. The diagnosis of a clinically nonfunctioning pancreatic neuroendocrine tumor was established by clinical and other studies, including USG-guided aspiration biopsy and octreotide scintigraphy, and the patient underwent a distal pancreatectomy. Histology proved a well-differentiated multinodular neuroendocrine tumor of the pancreas. During surgery, a subcutaneous lipoma was also removed from the abdominal wall. Two years later, the patient developed primary hyperparathyroidism, and two enlarged parathyroid glands were surgically removed. Magnetic resonance imaging of the pituitary gland was normal. Screening for MEN1 gene mutation by temperature gradient gel electrophoresis revealed heterozygosities in exons 3, 8, and 9, while direct sequencing indicated a novel germline mutation (C354X) resulting in a stop codon in exon 8 and polymorphisms in exon 3 (R171Q) and exon 9 (D418D and L432L). Genetic screening revealed no mutation in living family members. Our unusual case suggests that a multinodular pancreatic neuroendocrine tumor in a young patient may justify screening for MEN 1 syndrome, even in the absence of other endocrinopathy or family history.

MEN1 gene mutations in Hungarian patients with multiple endocrine neoplasia type 1

“…Four of these mutations have not been described previously. Two nonsense mutations (C354X and Q209X), two insertions (nt317ins5bp and nt1657insC) and two deletions (nt738del4 and nt359del4) have already been reported in our previous studies 24,26 . A screen for gene copy number alterations has not been performed in most studies on MEN1 including ours.…”

True MEN1 or phenocopy? Evidence for geno-phenotypic correlations in MEN1 syndrome

“…The c.202_206dupGCCCC mutation in exon 2 was identified in two probands. Ten mutations were described in our previous studies [13, 16], and further eight mutations have been reported formerly in the literature. To the best of our knowledge, of the 24 MEN1 gene mutations, five (c.19 C>T, p.Gln7STOP in exon 2; c.1160delA in exon 8; c.1399delG in exon 10; c.166_167insA in exon 2 and c.168delC in exon 2) have not yet been published, thus these were regarded as novel mutations (chromatograms of the mutated sequences can be found in Supplementary Fig.…”