Analysis of MEN1 c.482G>A (p.Gly161Asp) mutation in a pedigree with familial multiple endocrine neoplasia type 1

Luo,Yuanyuan; Sun,Yongxiang; Zhu,Xiaofan; Li,Xialian

doi:10.3892/mmr.2017.7749

Analysis of MEN1 c.482G>A (p.Gly161Asp) mutation in a pedigree with familial multiple endocrine neoplasia type 1

Authors:
- Yuanyuan Luo
- Yongxiang Sun
- Xiaofan Zhu
- Xialian Li
View Affiliations

Affiliations: Department of Endocrinology and Metabolism, Genetic and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Endocrinology and Geriatrics, The Medical Group of Zhengzhou First People's Hospital, Zhengzhou, Henan 450000, P.R. China
Published online on: October 10, 2017 https://doi.org/10.3892/mmr.2017.7749
Pages: 8973-8976

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the development of neuroendocrine tumors, which in turn are caused by mutations in the MEN1 gene. In the present study, a case of a 46‑year‑old woman who was clinically diagnosed with MEN1 based on the presence of prolactinoma and bilateral parathyroid adenoma was reported. The patient's serum prolactin (PRL) levels were successfully controlled via bromocriptine therapy, and the serum levels of calcium and intact parathyroid hormone (PTH) reduced one day following parathyroidectomy. Genetic testing revealed a missense mutation c.482G>A (p.Gly161Asp) in exon 3 of the MEN1 gene, and it led to the identification of two carriers in the pedigree (patient's elder sister and brother). Both of the carriers revealed to have high blood calcium, PTH and PRL. The mutation identified in this pedigree has never been reported in China. The sequence alignments and tertiary structure of menin protein were made by Polyphen2, SNPs3D, and SIFT, which were used to predict the function of mutant menin. Since the mutant menin may interfere with the menin‑JunD or menin‑Smad3 interactions, further investigations are necessary to explore the function of mutant protein. In view of that, identification of mutations and longtime follow‑up are important for patients with a pedigree clearly indicating MEN1.

View Figures

View References

1	Lemos MC and Thakker RV: Multiple endocrine neoplasia type 1 (MEN1): Analysis of 1336 mutations reported in the first decade following identification of the gene. Hum Mutat. 29:22–32. 2008. View Article : Google Scholar : PubMed/NCBI
2	Chandrasekharappa SC, Guru SC, Manickam P, Olufemi SE, Collins FS, Emmert-Buck MR, Debelenko LV, Zhuang Z, Lubensky IA, Liotta LA, et al: Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science. 276:404–407. 1997. View Article : Google Scholar : PubMed/NCBI
3	Concolino P, Costella A and Capoluongo E: Multiple endocrine neoplasia type 1 (MEN1): An update of 208 new germline variants reported in the last nine years. Cancer Genet. 209:36–41. 2016. View Article : Google Scholar : PubMed/NCBI
4	Stewart C, Parente F, Piehl F, Farnebo F, Quincey D, Silins G, Bergman L, Carle GF, Lemmens I, Grimmond S, et al: Characterization of the mouse Men1 gene and its expression during development. Oncogene. 17:2485–2493. 1998. View Article : Google Scholar : PubMed/NCBI
5	Mutch MG, Dilley WG, Sanjurjo F, DeBenedetti MK, Doherty GM, Wells SA Jr, Goodfellow PJ and Lairmore TC: Germline mutations in the multiple endocrine neoplasia type 1 gene: Evidence for frequent splicing defects. Hum Mutat. 13:175–185. 1999. View Article : Google Scholar : PubMed/NCBI
6	Guex N, Peitsch MC and Schwede T: Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: A historical perspective. Electrophoresis. 30 Suppl 1:S162–S173. 2009. View Article : Google Scholar : PubMed/NCBI
7	Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, Melmed S, Sakurai A, Tonelli F and Brandi ML: Endocrine Society: Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 97:2990–3011. 2012. View Article : Google Scholar : PubMed/NCBI
8	Guru SC, Goldsmith PK, Burns AL, Marx SJ, Spiegel AM, Collins FS and Chandrasekharappa SC: Menin, the product of the MEN1 gene, is a nuclear protein. Proc Natl Acad Sci USA. 95:pp. 1630–1634. 1998; View Article : Google Scholar : PubMed/NCBI
9	Huang J, Gurung B, Wan B, Matkar S, Veniaminova NA, Wan K, Merchant JL, Hua X and Lei M: The same pocket in menin binds both MLL and JUND but has opposite effects on transcription. Nature. 482:542–546. 2012. View Article : Google Scholar : PubMed/NCBI
10	Agarwal SK, Guru SC, Heppner C, Erdos MR, Collins RM, Park SY, Saggar S, Chandrasekharappa SC, Collins FS, Spiegel AM, et al: Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription. Cell. 96:143–152. 1999. View Article : Google Scholar : PubMed/NCBI
11	Pfarr CM, Mechta F, Spyrou G, Lallemand D, Carillo S and Yaniv M: Mouse JunD negatively regulates fibroblast growth and antagonizes transformation by ras. Cell. 76:747–760. 1994. View Article : Google Scholar : PubMed/NCBI
12	Thevenon J, Bourredjem A, Faivre L, Cardot-Bauters C, Calender A, Murat A, Giraud S, Niccoli P, Odou MF, Borson-Chazot F, et al: Higher risk of death among MEN1 patients with mutations in the JunD interacting domain: A Groupe d'Εtude des Tumeurs Endocrines (GTE) cohort study. Hum Mol Genet. 22:1940–1948. 2013. View Article : Google Scholar : PubMed/NCBI
13	Kaji H, Canaff L, Lebrun JJ, Goltzman D and Hendy GN: Inactivation of menin, a Smad3-interacting protein, blocks transforming growth factor type beta signaling. Proc Natl Acad Sci USA. 98:pp. 3837–3842. 2001; View Article : Google Scholar : PubMed/NCBI
14	Sowa H, Kaji H, Canaff L, Hendy GN, Tsukamoto T, Yamaguchi T, Miyazono K, Sugimoto T and Chihara K: Inactivation of menin, the product of the multiple endocrine neoplasia type 1 gene, inhibits the commitment of multipotential mesenchymal stem cells into the osteoblast lineage. J Biol Chem. 278:21058–21069. 2003. View Article : Google Scholar : PubMed/NCBI
15	Knudson AG Jr: Mutation and cancer: Statistical study of retinoblastoma. Proc Natl Acad Sci USA. 68:pp. 820–823. 1971; View Article : Google Scholar : PubMed/NCBI
16	Luzi E, Marini F, Giusti F, Galli G, Cavalli L and Brandi ML: The negative feedback-loop between the oncomir Mir-24-1 and menin modulates the Men1 tumorigenesis by mimicking the ‘Knudson's second hit’. PLoS One. 7:e397672012. View Article : Google Scholar : PubMed/NCBI
17	Falchetti A: Genetic screening for multiple endocrine neoplasia syndrome type 1 (MEN-1): When and how. F1000 Med Rep. 2:pii: 142010.