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A new frameshift MEN1 gene mutation associated with familial malignant insulinomas

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Abstract

MEN-1 is an autosomal dominant familial cancer syndrome characterized by involvement of parathyroid, enteropancreatic endocrine tissues and the anterior pituitary gland. Malignant insulinomas are rare, and therefore, there are few data regarding their clinical presentation and long-term prognosis. In this report we present a large family with malignant insulinoma and hyperparathyroidism with MEN-1 gene mutation analysis. A large family (three generations) with several members affected were evaluated for clinical and biochemical characteristic of MEN-1 syndrome. Genetic analysis for MEN1 gene was carried out in all family members using PCR amplification of coding regions followed by direct sequencing. In three brothers that presented with hypoglycemia, insulinoma was confirmed and two were malignant according to pathology and surgery report. Two of them had hyperparathyroidism too. Mutation screening revealed the presence of a two nucleotide deletion in the exon 2 (c199_200del2). In the current study, the deletion happens early in the sequence, and obviously results in a non-functional gene product. However, it will be helpful to further examine somatic mutations and other genetic markers for a more precise study of genotype-phenotype correlation.

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Acknowledgments

We gratefully thank this family for consenting to the publication of this study.

conflict of interest

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Authors and Affiliations

  1. Endocrinology and Metabolism Research Centre, Tehran University of Medical Sciences, 5th Floor, Shariati Hospital, North Kargar Ave, 14114, Tehran, Iran

    Shirin Hasani-Ranjbar, Mahsa M. Amoli, Azadeh Ebrahim-Habibi, Forugh A. Sayyahpour, Jila Hafeziyeh, Akbar Soltani & Bagher Larijani

  2. Endocrine Ward, Kerman University of Medical Sciences, Tehran, Iran

    Mohammad Hossein Gozashti

  3. Endocrine Ward, Baghiatalla University, Tehran, Iran

    Nahid Khalili

Authors
  1. Shirin Hasani-Ranjbar
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  2. Mahsa M. Amoli
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  3. Azadeh Ebrahim-Habibi
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  4. Mohammad Hossein Gozashti
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  5. Nahid Khalili
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  6. Forugh A. Sayyahpour
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  7. Jila Hafeziyeh
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  8. Akbar Soltani
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  9. Bagher Larijani
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Corresponding authors

Correspondence to Shirin Hasani-Ranjbar or Mahsa M. Amoli.

Additional information

Malignant insulinoma associated with MEN1 is very rare. We evaluated a large family with malignant insulinoma and hyperparathyroidism and found a novel frameshift germline mutation.

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Hasani-Ranjbar, S., Amoli, M.M., Ebrahim-Habibi, A. et al. A new frameshift MEN1 gene mutation associated with familial malignant insulinomas. Familial Cancer 10, 343–348 (2011). https://doi.org/10.1007/s10689-010-9412-z

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