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Horm Metab Res 2020; 52(11): 788-795
DOI: 10.1055/a-1147-1375
Endocrine Care

Identification of Novel Variants in MEN1: A Study Conducted with Four Multiple Endocrine Neoplasia Type 1 Patients

Wen-mu Hu
1   Department of Endocrinology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
,
Qin Zhang
1   Department of Endocrinology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
,
Li-hua Huang
1   Department of Endocrinology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
,
Zhao-hui Mo
1   Department of Endocrinology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
,
Xiao-dan Long
1   Department of Endocrinology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
,
You-bo Yang
1   Department of Endocrinology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
,
Wen-jun Yang
1   Department of Endocrinology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
,
Jun Liu
1   Department of Endocrinology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
,
Ping Jin
1   Department of Endocrinology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
› Institutsangaben Funding: This work was supported by the National Natural Science Foundation of China (81670730, 81100583).
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Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited endocrine tumor syndrome caused by inactivating variants of the MEN1 gene. The aim of this study is to explore the clinical and genetic characteristics of four MEN1 patients. We isolated genomic deoxyribonucleic acid from lymphocytes, parathyroid, and thymic tumoral tissue specimens from the MEN1 patients. All exons of the MEN1 and CDNK1B genes and adjacent exon-intron sequences were amplified by polymerase chain reaction and subsequently sequenced. Further, the splice alterations were studied by sequencing the amplified RT-PCR products for MEN1 cDNA. We identified four heterozygous MEN1 germline variants: c.564delC, c.1268G>A, IVS5+5delG, and c.1546_1547insC. Both c.564delC and IVS5+5delG were novel variants. The impact of the MEN1 splice variant, IVS5+5delG, was evaluated using bioinformatics and in vitro analyses. The analyses indicated that this variant resulted in skipping of the neighboring exon and was disease-causing. Two novel somatic variants, c.249_252delGTCT and c.313_314insC, were found. Additionally, loss of heterozygosity (LOH) for the MEN1 locus (IVS5+5delG and c.564delC) was found in tumor tissue samples from the MEN1 patients, consistent with Knudson’s two-hit mechanism. We identified four MEN1 germline variants and two novel somatic variants. Early recognition of the phenotype coupled with variant screening of the MEN1 gene is the key to diagnosing and treating MEN1 effectively at an early stage.

Key words:

multiple endocrine neoplasia type 1 - adenomas - variant

Supplementary Material



Publikationsverlauf

Eingereicht: 05. Februar 2020

Angenommen nach Revision: 18. März 2020

Artikel online veröffentlicht:
16. April 2020

© 2020. Thieme. All rights reserved.

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