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Kim, Kim, Shin, Kim, Na, Park, Lee, Koh, Lee, Song, Park, Lee, Kim, Yoo, and Kim: A Case of Familial Multiple Endocrine Neoplasia Type 1 with a Novel Mutation in the MEN1 Gene
Case Report
Endocrinology and Metabolism

Endocrinology and Metabolism 2011; 26(2): 171-176.

Published online: 30 June 2011

DOI: https://doi.org/10.3803/EnM.2011.26.2.171

A Case of Familial Multiple Endocrine Neoplasia Type 1 with a Novel Mutation in the MEN1 Gene

Min Jung Kim, Eun Hee Kim, Mi-Seon Shin, Joo Hui Kim, Hee Kyung Na, Seong Joon Park, Sang Ah Lee, Eun Hee Koh, Woo Je Lee, Ki Ho Song1, Joong-Yeol Park, Ki-Up Lee, Gu-Hwan Kim2, Han-Wook Yoo3, Min-Seon Kim

Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea.

1Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea.

2Medical Genetics Clinics and Laboratory, University of Ulsan College of Medicine, Seoul, Korea.

3Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea.

Corresponding author: Min-Seon Kim, Department of Internal Medicine, University of Ulsan College of Medicine, 388-1 Poongnap-dong, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-3245, Fax: 82-2-3010-6962, mskim@amc.seoul.kr

Received 17 June 2010       Accepted 1 November 2010

Copyright © 2011 Korean Endocrine Society

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the occurrence of multiple tumors in the parathyroid gland, pancreatic islet, and pituitary gland. This condition is caused by mutations of MEN1, a tumor suppressor gene. Thus far, 565 different germline and somatic mutations of the MEN1 gene have been reported. Herein, we describe the case of a 23-year-old woman who suffered from a repetitive loss of consciousness. After workup, the patient was diagnosed with MEN1 with insulinoma, hyperparathyrodism due to parathyroid adenoma, and non-functioning pituitary microadenoma. She underwent a partial parathyroidectomy and distal pancreatectomy. Familial screening of MEN1 revealed that her brother had prolactinoma, hyperparathyroidism, pancreatic gastrinoma and non-functioning adrenal adenoma. Her father had hyperparathyroidism, pancreatic tumor, and adrenal adenoma. Upon genetic analysis of the MEN1 gene, a novel mutation in the MEN1 gene (exon 1, c.251del; p.Ser84LuefsX35) was detected in the patient, as well as her father and brother.

Keywords: Multiple endocrine neoplasia type 1, Insulinoma, Hyperparathyroidism

Figures and Tables

Fig. 1
Abdominal computed tomography. A. 2 cm and 0.8 cm sized hypervascular masses (arrows) in pancreas body and tail in the patients. B. 1.5 cm sized hypervascular nodule in pancreas tail in the patient's brother. C. 1.8 cm sized cystic mass (arrow) in pancreas body and tail in the patient's father. D. 4 cm sized mass in left adrenal gland in the patient's brother. E. 1.5 cm sized nodule (arrow) in right adrenal gland in the patient's father.
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Fig. 2
Parathyroid gland scintigraphy using Tc-99m Sestamibi. A. The early image (10 minutes) showed focal increased uptake in left lower pole. In delayed image (2 hours), abnormal radioactivity accumulation in left lower pole was remained after washout of the thyroid gland activity, suggesting parathyroid adenoma in the patient. B. Two focal increased uptakes in upper and lower pole of right thyroid gland in the patient's brother. C. Two focal increased uptakes in posterior portion of left thyroid gland in the patient's father.
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Fig. 3
Sellar magnetic resonance imaging. A. 0.9 cm sized solid mass (arrow) in body and left wing of pituitary gland in the patient. B. 2.2 cm sized lobulating mass (arrow) in sellar and suprasellar area in the patient's brother.
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Fig. 4
Sequencing of exon 1 in the MEN1 gene showed a frameshift mutation caused by deletion at nucleotide c.251(p.Ser84LeufsX35).
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Fig. 5
Family pedigree. Individuals are represented as males (squares) and females (circles). Filled in symbols indicate affected family members, grey symbol indicates "probably affected" individual (unavailable for examination), clear symbols indicate unaffected family members. The proband is indicated by an asterisk.
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References

1. Park JH, Kim IJ, Kang HC, Lee SH, Shin Y, Kim KH, Lim SB, Kang SB, Lee K, Kim SY, Lee MS, Lee MK, Moon SD, Park JG. Germline mutations of the MEN1 gene in Korean families with multiple endocrine neoplasia type 1 (MEN1) or MEN1-related disorders. Clin Genet. 2003. 64:48–53.
2. Park SE, Kang ES, Lee HJ, Kim SH, Do MY, Kang SA, Han SJ, Kim HJ, Ahn CW, Cha BS, Lim SK, Kim KR, Kim IJ, Lee HC. A case of multiple endocrine neoplasia type 1 with mutation in MENIN gene. J Korean Soc Endocrinol. 2005. 20:71–77.
3. Lee KD, Kim JY, Mun HS, Choi SH, Lee HH, Choi YS, Park YH, Uchino S. Menin mutational analysis in a MEN I family. Korean J Otolaryngol-Head Neck Surg. 2005. 48:347–351.
4. Marx SJ, Agarwal SK, Kester MB, Heppner C, Kim YS, Skarulis MC, James LA, Goldsmith PK, Saggar SK, Park SY, Spiegel AM, Burns AL, Debelenko LV, Zhuang Z, Lubensky IA, Liotta LA, Emmert-Buck MR, Guru SC, Manickam P, Crabtree J, Erdos MR, Collins FS, Chandrasekharappa SC. Multiple endocrine neoplasia type 1: clinical and genetic features of the hereditary endocrine neoplasias. Recent Prog Horm Res. 1999. 54:397–438.
5. Rasbach DA, van Heerden JA, Telander RL, Grant CS, Carney JA. Surgical management of hyperinsulinism in the multiple endocrine neoplasia, type 1 syndrome. Arch Surg. 1985. 120:584–589.
6. Trump D, Farren B, Wooding C, Pang JT, Besser GM, Buchanan KD, Edwards CR, Heath DA, Jackson CE, Jansen S, Lips K, Monson JP, O'Halloran D, Sampson J, Shalet SM, Wheeler MH, Zink A, Thakker RV. Clinical studies of multiple endocrine neoplasia type 1 (MEN1). QJM. 1996. 89:653–669.
7. Larsson C, Skogseid B, Oberg K, Nakamura Y, Nordenskjold M. Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature. 1988. 332:85–87.
8. Lemos MC, Thakker RV. Multiple endocrine neoplasia type 1 (MEN1): analysis of 1336 mutations reported in the first decade following identification of the gene. Hum Mutat. 2008. 29:22–32.
9. Chae YS, Kim HJ, Kim SW, Chang MC. Somatic mutational analysis of MEN1 and phenotypic correlation in sporadic parathyroid tumors. J Korean Surg Soc. 2009. 76:15–22.
10. Pannett AA, Thakker RV. Multiple endocrine neoplasia type 1. Endocr Relat Cancer. 1999. 6:449–473.
11. Brandi ML, Marx SJ, Aurbach GD, Fitzpatrick LA. Familial multiple endocrine neoplasia type I: a new look at pathophysiology. Endocr Rev. 1987. 8:391–405.
12. Uchino S, Noguchi S, Sato M, Yamashita H, Watanabe S, Murakami T, Toda M, Ohshima A, Futata T, Mizukoshi T, Koike E, Takatsu K, Terao K, Wakiya S, Nagatomo M, Adachi M. Screening of the Men1 gene and discovery of germ-line and somatic mutations in apparently sporadic parathyroid tumors. Cancer Res. 2000. 60:5553–5557.
13. Scarpelli D, D'Aloiso L, Arturi F, Scillitani A, Presta I, Bisceglia M, Cristofaro C, Russo D, Filetti S. Novel somatic MEN1 gene alterations in sporadic primary hyperparathyroidism and correlation with clinical characteristics. J Endocrinol Invest. 2004. 27:1015–1021.
14. Goebel SU, Heppner C, Burns AL, Marx SJ, Spiegel AM, Zhuang Z, Lubensky IA, Gibril F, Jensen RT, Serrano J. Genotype/phenotype correlation of multiple endocrine neoplasia type 1 gene mutations in sporadic gastrinomas. J Clin Endocrinol Metab. 2000. 85:116–123.
15. Schussheim DH, Skarulis MC, Agarwal SK, Simonds WF, Burns AL, Spiegel AM, Marx SJ. Multiple endocrine neoplasia type 1: new clinical and basic findings. Trends Endocrinol Metab. 2001. 12:173–178.
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