Multiple Endocrine Neoplasia Type 1: A Chinese Family with a new germline mutation(c.201delC) and A Detection Errors due to Intron Mutation

Abstract

Background: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary cancer syndrome caused by germline mutations in the MEN1 gene located on chromosome 11q13. The three main endocrine tissues affected most frequently by tumors in MEN1 are the parathyroid (95%), enteropancreatic neuroendocrine tissues (50%), and anterior pituitary (40%). The purpose of this study was to report on a Chinese family with a new heterozygous MEN1 mutation in exon 2 [NM_130802: c.201delC (p.Ala68Profs*51) with localization to Chr11:64577381 on assembly GRCh37].Methods: A 49-year-old female patient (proband) was admitted to the hospital due to intermittent recurrent hypoglycemia symptoms. After a series of examinations, we found that she had a pancreatic tumor, parathyroid tumor, adrenal tumor, and suspicious gastrinoma. Due to the proband’s suspicious clinical manifestations of MEN1, we performed genetic detection for the proband and her immediate family members. To rule out homozygous mutations caused by deletion of gene fragments, the proband and her immediate family members were detected the MLPA (Multiplex ligation-dependent probe amplification).Results: A new MEN1 germline mutation [c.201delC (p.Ala68Profs*51)], which could induce MEN1, was found by the genetic test. Two of the proband’s six relatives were found by the genetic test to have the same mutations as the proband, and the proband’s sister has the typical symptoms of MEN1 as well. However, the first time and second time genetic detection results showed that they were homozygous mutation, it didn’t conform to Mendelian inheritance laws. The MLPA results showed that the gene deletion was absent in the MEN1. The third time genetic detection (redesigned the prime) showed that they were heterozygous mutation. This detection errors due to intron mutation.Conclusions: A new germline mutation that induced MEN1, which can improve the identification of clinical phenotypes of MEN1 and the early diagnosis of the disease, was identified. Intron mutation may lead to wrong results of homozygous, which incompatible with Mendelian genetic law. Redesign the primer for gene detection could avoid this situation.