ArticleEndocrine connections2015
Functional characterization of a CDKN1B mutation in a Sardinian kindred with multiple endocrine neoplasia type 4 (MEN4).
Article in Endocrine connections, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Neuroendocrine Tumors: Germline Genetics and Hereditary Syndromes.Current treatment options in oncology · 2025Review
- Familial states of primary hyperparathyroidism: an update.Journal of endocrinological investigation · 2024Review
- Performance in Behavioral Testing in an Animal Model of Post-Surgical Hypoparathyroidism.Journal of personalized medicine · 2024Article
- Challenges in molecular diagnosis of multiple endocrine neoplasia.Frontiers in endocrinology · 2024Review
- Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism.Journal of endocrinological investigation · 2023Article
- Multiple endocrine neoplasia type 4: a new member of the MEN family.Endocrine connections · 2023Article
- MEN4, the MEN1 Mimicker: A Case Series of three Phenotypically Heterogenous Patients With Unique CDKN1B Mutations.The Journal of clinical endocrinology and metabolism · 2022Article
- Case Report: New CDKN1B Mutation in Multiple Endocrine Neoplasia Type 4 and Brief Literature Review on Clinical Management.Frontiers in endocrinology · 2022Review
- Hereditary Parathyroid Disease: Sometimes Pathologists Do Not Know What They Are Missing.Endocrine pathology · 2020Review
- Inherited syndromes involving pancreatic neuroendocrine tumors.Journal of gastrointestinal oncology · 2020Review
- Germline CDKN1B Loss-of-Function Variants Cause Pediatric Cushing's Disease With or Without an MEN4 Phenotype.The Journal of clinical endocrinology and metabolism · 2020Article
- Clinical Features of Multiple Endocrine Neoplasia Type 4: Novel Pathogenic Variant and Review of Published Cases.The Journal of clinical endocrinology and metabolism · 2019Review
- Genetics of Cushing's Syndrome.Endocrinology and metabolism clinics of North America · 2018Review
- Landscape of CDKN1B Mutations in Luminal Breast Cancer and Other Hormone-Driven Human Tumors.Frontiers in endocrinology · 2018Review
- MEN4 andEndocrine-related cancer · 2017Review
- MEN1 mutations and potentially MEN1-targeting miRNAs are responsible for menin deficiency in sporadic and MEN1 syndrome-associated primary hyperparathyroidism.Virchows Archiv : an international journal of pathology · 2017Article
- Loss of p27 expression is associated with MEN1 gene mutations in sporadic parathyroid adenomas.Endocrine · 2017Article
- Article
- Animal models of pituitary neoplasia.Molecular and cellular endocrinology · 2016Review
- An unusual phenotype of MEN1 syndrome with a SI-NEN associated with a deletion of the MEN1 gene.Endocrinology, diabetes & metabolism case reports · 2016Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inactivating germline mutations of the CDKN1B gene, encoding for the nuclear cyclin-dependent kinase inhibitor p27kip1 protein, have been reported in patients with multiple endocrine neoplasia type 4 (MEN4), a MEN1-like phenotype without MEN1 mutations. The aim of this study was to in vitro characterize the germline CDKN1B mutation c.374_375delCT (S125X) we detected in a patient with MEN4. The proband was affected by multiglandular primary hyperparathyroidism and gastro-entero-pancreatic tumors. We carried out subcellular localization experiments transfecting into eukaryotic HeLa and GH3 cell lines plasmid vectors expressing the CDKN1B wild type (wt) or mutant cDNA. Western blot studies showed that fusion proteins were expressed at equal levels. The mutated protein was shorter compared to the wt protein and lacked the highly conserved C-terminal domain, which includes the bipartite nuclear localization signal at amino acids 152/153 and 166/168. In HeLa and GH3 cells wt p27 localized in the nucleus whereas the p27_S125X protein was retained in the cytoplasm predicting the loss of tumor suppressive function. The proband's tumoral parathyroid tissue did not show allelic loss, since wt and mutant alleles were both present by sequencing the somatic DNA. Immunohistochemistry showed a complete loss of nuclear p27 expression in the parathyroid adenoma removed by the patient at the second surgery. In conclusion, our study confirms the pathogenic role of the c.374_375delCT CDKN1B germline mutation in a patient with MEN4.
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