A large Turkish pedigree with multiple endocrine neoplasia type 1 syndrome carrying a rare mutation: c.1680_1683 del TGAG

Background/Aims: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome characterized by tumors arising from endocrine glands with no specific genotype-phenotype correlation. Here, we report the largest Turkish kindred with MEN1 syndrome which inherited a scarce MEN1 mutation gene. Materials and Methods: A 64-year-old man, referred to our gastroenterology outpatient clinic for evaluation of a pancreatic mass lesion, was diagnosed with MEN1 syndrome after endoscopic ultrasound-guided sampling of the mass revealed pancreatic neuroendocrine tumor (pNET) and accompanying primary hyperparathyroidism (PHPT) and pituitary tumor. Genetic analysis by whole gene Sanger sequencing of the MEN1 gene identified a frame-shift mutation in exon 10 (c.1680_1683delTGAG). All the relatives of the index case were proposed for clinical and genetic evaluation for MEN1 syndrome.Results: Of the 25 relatives of the index case, 17 were diagnosed with the MEN1 syndrome. Eighteen members among all relatives consented to genetic analysis, and 11 had the same mutation as the index case. All the mutation positive members had MEN1, while none of mutation-negative subjects had any sign of MEN1 syndrome. The frequencies of PHPT, pNET, and pituitary tumors in this kindred were 94.1% (16/17), 29.4% (5/17), and 29.4% (5/17) respectively.Conclusion: We report a rare MEN1 gene mutation which has been descibed in a single sporadic patient earlier. It was inherited by at least three generations of a large family, proving the strong dominant effect of the MEN1 phenotype. Further research may be conducted to clarify potential candidacy of this mutation as a hotspot for MEN1 patients, especially in the Turkish population.


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