TY  - JOUR
A1  - Welsch, Christoph
A1  - Flügel, Anna Katharina
A1  - Rondot, Susanne
A1  - Schulze, Egbert
A1  - Sircar, Ishani
A1  - Nußbaumer, Judith
A1  - Bojunga, Jörg
T1  - Distinct clinical phenotypes in a family with a novel truncating MEN1 frameshift mutation
T2  - BMC endocrine disorders
N2  - Background: MEN1 mutations can inactivate or disrupt menin function and are leading to multiple endocrine neoplasia type 1, a rare heritable tumor syndrome.
Case presentation: We report on a MEN1 family with a novel heterozygous germline mutation, c.674delG; p.Gly225Aspfs*56 in exon 4 of the MEN1 gene. Diagnosis and clinical phenotyping of MEN1 was established by laboratory tests, ultrasound, biopsy, MRI imaging and endosonography. The clinical course of the disease was followed in the index patient and her family members for eight years. The mutation was associated with distinct clinical phenotypes in the index patient and three family members harboring p.Gly225Aspfs*56. Family members affected showed primary hyperparathyroidism but variable patterns of associated endocrine tumors, adrenal cortical adenomas, prolactinoma, multifocal pancreatic neuroendocrine tumors, insulinoma and nonsecretory neuroendocrine tumors of the pancreas. The mutation c.674delG; p.Gly225Aspfs*56 leads to a frameshift from codon 225 with early truncation of the menin protein. In silico analysis predicts loss of multiple protein-menin interactions in p.Gly225Aspfs*56, potentially rendering menin insufficient to control cell division and replication. However, no aggressive neuroendocrine tumors were observed in the follow-up of this family.
Conclusions: We report a novel heterozygous MEN1 frameshift mutation, potentially causing (at least partial) inactivation of menin tumor suppression potential but lacking a genotype–phenotype correlation. Our study highlights the importance of personalized care with appropriate testing and counseling in MEN1 families.
KW  - Case report
KW  - MEN1
KW  - Truncating mutation
KW  - Frameshift
KW  - Clinical phenotype
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/69512
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-695127
SN  - 1472-6823
N1  - Open Access funding enabled and organized by Projekt DEAL.
VL  - 22
IS  - art. 64
SP  - 1
EP  - 8
PB  - BioMed Central
CY  - [Erscheinungsort nicht ermittelbar]
ER  -