Identification of a novel frameshift c.930delG MEN1 germline mutation (p.Glu273LysfsTer7) in a sporadic case of multiple endocrine neoplasia type 1: A case report

Naruse,Hiromu; Umemura,Hiroshi; Nakayama,Tomohiro

doi:10.3892/mmr.2020.11596

Identification of a novel frameshift c.930delG MEN1 germline mutation (p.Glu273LysfsTer7) in a sporadic case of multiple endocrine neoplasia type 1: A case report

Authors:
- Hiromu Naruse
- Hiroshi Umemura
- Tomohiro Nakayama
View Affiliations

Affiliations: Division of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 173‑8610, Japan
Published online on: October 14, 2020 https://doi.org/10.3892/mmr.2020.11596
Pages: 5423-5427

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 a rare genetic disorder that is inherited in an autosomal dominant manner. The characteristics of the disease are the combined occurrence of tumors in glands of the endocrine system, such as the parathyroid glands, pituitary gland and endocrine pancreas. Germline mutations in the MEN1 gene are associated with the occurrence of MEN1 and genetic testing for this gene is generally used as a basis for diagnosis. In this paper, a case of MEN1 in a middle‑aged Japanese woman is reported. Direct sequencing analysis of the patient's DNA was performed and it revealed a MEN1 gene heterozygous germline (NM_130799.2:c.930delG) mutation in exon 5. This deletion/frameshift mutation produced a stop codon in the downstream sequence (NP_570711.1:p.Glu273LysfsTer7). To the best of our knowledge, this is the first report describing the NM_130799.2:c.930delG mutation as the basis for MEN1.

View Figures

View References

1	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
2	Mark SJ: Recent topics around multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 103:1296–1301. 2018. View Article : Google Scholar : PubMed/NCBI
3	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
4	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. 95:1630–1634. 1998. View Article : Google Scholar : PubMed/NCBI
5	Canaff L, Vanbellinghen JF, Kaji H, Goltzman D and Hendy GN: Impaired transforming growth factor-β (TGF-β) transcriptional activity and cell proliferation control of a menin in-frame deletion mutant associated with multiple endocrine neoplasia type 1 (MEN1). J Biol Chem. 287:8584–8597. 2012. View Article : Google Scholar : PubMed/NCBI
6	Hyde SM, Cote GJ and Grubbs EG: Genetics of multiple endocrine neoplasia type 1/multiple endocrine neoplasia type 2 syndromes. Endocrinol Metab Clin North Am. 46:491–502. 2017. View Article : Google Scholar : PubMed/NCBI
7	Luo Y, Sun Y, Zhu X and Li X: Analysis of MEN1 c.482G>A (p.Gly161Asp) mutation in a pedigree with familial multiple endocrine neoplasia type 1. Mol Med Rep. 16:8973–8976. 2017. View Article : Google Scholar : PubMed/NCBI
8	Bennett RL, French KS, Resta RG and Doyle DL: Standardized human pedigree nomenclature: Update and assessment of the recommendations of the National Society of Genetic Counselors. J Genet Couns. 17:424–433. 2008. View Article : Google Scholar : PubMed/NCBI
9	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
10	Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C, Conte-Devolx B, Falchetti A, Gheri RG, Libroia A, et al: Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 86:5658–5671. 2001. View Article : Google Scholar : PubMed/NCBI
11	Hai N, Aoki N, Shimatsu A, Mori T and Kosugi S: Clinical features of multiple endocrine neoplasia type 1 (MEN1) phenocopy without germline MEN1 gene mutations: Analysis of 20 Japanese sporadic cases with MEN1. Clin Endocrinol (Oxf). 52:509–518. 2000. View Article : Google Scholar : PubMed/NCBI
12	De Laat JM, van der Luijt RB, Pieterman CR, Oostveen MP, Hermus AR, Dekkers OM, de Herder WW, van der Horst-Schrivers AN, Drent ML, Bisschop PH, et al: MEN1 redefined, a clinical comparison of mutation-positive and mutation-negative patients. BMC Med. 14:1822016. View Article : Google Scholar : PubMed/NCBI
13	Ellard S, Hattersley AT, Brewer CM and Vaidya B: Detection of an MEN1 gene mutation depends on clinical features and supports current referral criteria for diagnostic molecular genetic testing. Clin Endocrinol (Oxf). 62:169–175. 2005. View Article : Google Scholar : PubMed/NCBI
14	Marini F, Falchetti A, Del Monte F, Carbonell Sala S, Gozzini A, Luzi E and Brandi ML: Multiple endocrine neoplasia type 1. Orphanet J Rare Dis. 1:382006. View Article : Google Scholar : PubMed/NCBI
15	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
16	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