Application of an intracellular stability test of a novel missense menin mutant to the diagnosis of multiple endocrine neoplasia type 1

Endocrine Journal

Satoko Shimazu²  Masanori Yamazaki¹  Akihiro Sakurai¹  Toshihiko Tsukada²  Yuko Nagamura² 

[1] Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan;Division of Familial Cancer Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan

关键词: MEN1;    Menin;    Stability;    Missense mutation;   

DOI  :  10.1507/endocrj.EJ12-0145

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(19)Cited-By(2)Germline MEN1 mutation analysis is a powerful tool for an early diagnosis of multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant familial cancer syndrome characterized by the parathyroid, pituitary and gastroenteropancreatic endocrine tumors.However, the clinical significance of MEN1 gene variants, especially missense and in-frame mutations as well as some splicing mutations, is not always obvious.We have previously shown that mutant menin proteins associated with MEN1 are rapidly degraded by the ubiquitin-proteasome pathway.We also demonstrated by a fluorescent immunocytochemical stability test that the stability of missense and in-frame deletion mutants varies widely but that unstable mutants were found only in MEN1 and related disorders and not in normal polymorphisms.In the present study, we evaluated by this stability test the pathogenicity of a novel MEN1 missense mutation, c.1118C>T, encoding a P373L mutant menin, identified in a suspected MEN1 patient.The results demonstrated that the mutant menin is highly unstable, indicating that this mutation is causative for MEN1.These findings encouraged us to proceed with presymptomatic genetic screening for this mutation among the family members, which resulted in the identification of asymptomatic mutation carriers.Thus, the information from the menin stability test was useful for genetic diagnosis and counseling of MEN1 in the case with a previously unreported MEN1 missense mutation.

【 授权许可】

Unknown