Identification of a germline mutation in the HRPT2 gene in a Chinese family with parathyroid carcinomas

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. We also used multiplex ligation-dependent probe amplification (MLPA) to rule out homozygous mutations caused by a deletion of gene fragments in the proband and her immediate family members. 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 also had the typical symptoms of MEN1. However, the first and second genetic detection results showed that they were homozygous mutations, which did not conform to Mendelian inheritance laws. The MLPA results showed that the gene deletion was absent in the MEN1. The results from the third genetic detection (redesigned the primer) showed that they had a heterozygous mutation. The detection errors might due to an intron mutation. Conclusions: A new germline mutation, which can improve the identification of clinical phenotypes and the early diagnosis of MEN1, was identified. An intron mutation may lead to incorrect results of homozygous, which is incompatible with Mendelian genetic law. Redesigning the primers for gene detection could avoid this situation.

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

10.21203/rs.3.rs-41525/v2 ◽

2020 ◽

Author(s):

Fan Zhang ◽

Xinyue Lin ◽

Xiaoli Wang ◽

Xiaohui Yu

Keyword(s):

Germline Mutation ◽

Multiple Endocrine Neoplasia ◽

Multiple Endocrine Neoplasia Type ◽

Genetic Test ◽

Chinese Family ◽

Endocrine Neoplasia ◽

Genetic Detection ◽

Homozygous Mutations ◽

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 a suspicious gastrinoma. Due to the proband’s suspicious clinical manifestations of MEN1, we performed genetic detection for the proband and her immediate family members. We also used multiplex ligation-dependent probe amplification (MLPA) to rule out homozygous mutations caused by a deletion of gene fragments in the proband and her immediate family members.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 also had the typical symptoms of MEN1. However, the first and second genetic detection results showed that they were homozygous mutations, which did not conform to Mendelian inheritance laws. The MLPA results showed that the gene deletion was absent in the MEN1. The results from the third genetic detection (redesigned the primer) showed that they were a heterozygous mutation. The detection errors were due to an 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. An intron mutation may lead to incorrect results of homozygous, which is incompatible with Mendelian genetic law. Redesigning the primers for gene detection could avoid this situation.

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One germline mutation of PTCH gene in a Chinese family with non-syndromic keratocystic odontogenic tumours

International Journal of Oral and Maxillofacial Surgery ◽

10.1016/j.ijom.2011.03.012 ◽

2011 ◽

Vol 40 (8) ◽

pp. 829-833 ◽

Cited By ~ 2

Author(s):

X. Wang ◽

Y. Lu ◽

G. Shen ◽

W. Chen

Keyword(s):

Germline Mutation ◽

Chinese Family ◽

Odontogenic Tumours

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

10.21203/rs.3.rs-41525/v1 ◽

2020 ◽

Author(s):

Fan Zhang ◽

Xinyue Lin ◽

Xiaoli Wang ◽

Xiaohui Yu

Keyword(s):

Germline Mutation ◽

Multiple Endocrine Neoplasia ◽

Multiple Endocrine Neoplasia Type ◽

Genetic Test ◽

Family Members ◽

Chinese Family ◽

Endocrine Neoplasia ◽

Genetic Detection ◽

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.

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