Research Papers: Chromosome:
Long-term follow-up and novel splice donor mutation in MEN1 in a Chinese family
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Minghao Li1,*, Qianqian Liu2,*, Peihua Liu1, Xiaoping Yi3, Xiao Guan1, Anze Yu1, Longfei Liu1,# and Feizhou Zhu2,4,#
1Department of Urology, Xiangya Hospital, Central South University, Changsha, China
2Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, Changsha, China
3Department of Radiology, Xiangya Hospital, Central South University, Changsha, China
4Xiangya Hospital, Central South University, Changsha, China
*These authors contributed equally to this work
#These authors are joint senior authors
Longfei Liu, email: [email protected]
Feizhou Zhu, email: [email protected]
Keywords: multiple endocrine neoplasia type 1; MEN1 gene; splicing site mutation; somatic mutation
Received: May 10, 2017 Accepted: November 16, 2017 Published: December 07, 2017
Heterozygous germline mutation of the MEN1 tumor suppressor gene is responsible for multiple endocrine neoplasia type 1. Parathyroid and thoracic neuroendocrine tumor specimens and DNA from two Han Chinese MEN1 family patients were analyzed using whole exome and Sanger sequencing. The proband (II-3) was sequentially diagnosed with pituitary adenoma, pancreatic tumor, adrenal cortical tumor, abdominal lipoma, and parathyroid adenoma during the 6-year follow-up. The son of the proband (III-6) was also diagnosed with a thoracic neuroendocrine tumor and a parathyroid adenoma during this period. Splice alterations were studied by RT-PCR and sequencing. The mutation impact was evaluated using bioinformatics. Sequence analysis revealed a novel splice donor mutation, MEN1 IVS9 + 1G > C, that changed the splicing mode of MEN1 to halt translation before two nuclear localization signals in the menin protein. Novel somatic mutations, MEN1 c.1402_1405delGAGG and c.286 C > T, were identified in the parathyroid adenoma of II-3 and thoracic neuroendocrine tumor of III-6, respectively, indicating a two-hit etiology of MEN1 syndrome. Our study revealed the clinical and genetic basis of MEN1 in this Han Chinese family and provides insight into MEN1 mechanisms, diagnosis, and management.
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