Distinct clinical phenotypes in a family with a novel truncating MEN1 frameshift mutation
Abstract 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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-03-01
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| Series: | BMC Endocrine Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12902-022-00978-9 |
| _version_ | 1829117855644254208 |
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| author | Christoph Welsch Anna Katharina Flügel Susanne Rondot Egbert Schulze Ishani Sircar Judith Nußbaumer Jörg Bojunga |
| author_facet | Christoph Welsch Anna Katharina Flügel Susanne Rondot Egbert Schulze Ishani Sircar Judith Nußbaumer Jörg Bojunga |
| author_sort | Christoph Welsch |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-13T10:09:53Z |
| format | Article |
| id | doaj.art-c9e0cebbdff3403aa9dbefd8687f8b95 |
| institution | Directory Open Access Journal |
| issn | 1472-6823 |
| language | English |
| last_indexed | 2024-12-13T10:09:53Z |
| publishDate | 2022-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Endocrine Disorders |
| spelling | doaj.art-c9e0cebbdff3403aa9dbefd8687f8b952022-12-21T23:51:28ZengBMCBMC Endocrine Disorders1472-68232022-03-012211810.1186/s12902-022-00978-9Distinct clinical phenotypes in a family with a novel truncating MEN1 frameshift mutationChristoph Welsch0Anna Katharina Flügel1Susanne Rondot2Egbert Schulze3Ishani Sircar4Judith Nußbaumer5Jörg Bojunga6Department of Internal Medicine 1, Goethe-University Hospital FrankfurtDepartment of Internal Medicine 1, Goethe-University Hospital FrankfurtMVZ Labor Dr. Limbach & Kollegen GbRMVZ Labor Dr. Limbach & Kollegen GbRDepartment of Internal Medicine 1, Goethe-University Hospital FrankfurtDepartment of Internal Medicine 1, Goethe-University Hospital FrankfurtDepartment of Internal Medicine 1, Goethe-University Hospital FrankfurtAbstract 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.https://doi.org/10.1186/s12902-022-00978-9Case reportMEN1Truncating mutationFrameshiftClinical phenotype |
| spellingShingle | Christoph Welsch Anna Katharina Flügel Susanne Rondot Egbert Schulze Ishani Sircar Judith Nußbaumer Jörg Bojunga Distinct clinical phenotypes in a family with a novel truncating MEN1 frameshift mutation BMC Endocrine Disorders Case report MEN1 Truncating mutation Frameshift Clinical phenotype |
| title | Distinct clinical phenotypes in a family with a novel truncating MEN1 frameshift mutation |
| title_full | Distinct clinical phenotypes in a family with a novel truncating MEN1 frameshift mutation |
| title_fullStr | Distinct clinical phenotypes in a family with a novel truncating MEN1 frameshift mutation |
| title_full_unstemmed | Distinct clinical phenotypes in a family with a novel truncating MEN1 frameshift mutation |
| title_short | Distinct clinical phenotypes in a family with a novel truncating MEN1 frameshift mutation |
| title_sort | distinct clinical phenotypes in a family with a novel truncating men1 frameshift mutation |
| topic | Case report MEN1 Truncating mutation Frameshift Clinical phenotype |
| url | https://doi.org/10.1186/s12902-022-00978-9 |
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