Evidence mapPaperPMID 40128946Full record

ArticleThe Journal of clinical endocrinology and metabolism2025

Prevalence and genetics of "de novo" MEN2 syndromes.

Roberta Casalini, Cristina Romei, Valeria Bottici, Virginia Cappagli, Valeria Tascini, Antonio Matrone, Alessandro Prete, Raffaele Ciampi, Teresa Ramone, Rossella Elisei

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Article in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

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4citing papers in PubMed
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1 · What the graph read from it

What it found

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3 · Its place in the literature

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4 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Roberta CasaliniDepartment of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, 56100 Pisa, Italy.ORCID 0009-0001-6017-5166
Cristina RomeiDepartment of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, 56100 Pisa, Italy.ORCID 0000-0002-5957-8902
Valeria BotticiDepartment of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, 56100 Pisa, Italy.
Virginia CappagliDepartment of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, 56100 Pisa, Italy.
Valeria TasciniDepartment of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, 56100 Pisa, Italy.
Antonio MatroneDepartment of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, 56100 Pisa, Italy.
Alessandro PreteDepartment of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, 56100 Pisa, Italy.ORCID 0000-0003-3633-6916
Raffaele CiampiDepartment of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, 56100 Pisa, Italy.ORCID 0000-0001-6345-9343
Teresa RamoneDepartment of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, 56100 Pisa, Italy.
Rossella EliseiDepartment of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, 56100 Pisa, Italy.ORCID 0000-0002-5333-9257

Funding

Associazione Italiana per la Ricerca sul CancroProgetti di Ricerca di Ateneo, University of Pisa PRA_2022_51
6 · The paper itself

Abstract

contextHereditary medullary thyroid carcinoma (MTC) is an inherited syndrome accounting for 25% of MTC cases. It is caused by germline RET mutations, which can be inherited or occur de novo.

objectiveThis study aimed to define the prevalence and genetics of de novo MEN2 syndromes, which are not yet fully understood, and to characterize the parental origin of the RET de novo mutation.

methodsWe selected 152 of 215 families with hereditary MTC. In de novo cases, we sequenced the wild-type and mutated alleles of the index cases and compared their single nucleotide polymorphism profiles with those of their parents. Digital droplet PCR was performed to determine the presence of mosaicism in both the index case and the parents.

resultsIn 24 of 152 (15.78%) families, the index case had a de novo mutation. Single nucleotide polymorphism analysis demonstrated that in all cases, the mutation occurred on the paternal allele. The absence of mosaicism supported the hypothesis that the mutation occurred during spermatogenesis. The mean age of fathers at the time of conception was, in some cases but not all, relatively advanced.

conclusionThe prevalence of de novo hereditary MEN2 syndromes was approximately 16%, including MEN2B, and around 9% for other phenotypes. All de novo cases were of paternal origin and likely resulted from an acquired alteration in sperm DNA. The possible role of advanced paternal age in promoting de novo mutations could not be ruled out.

Indexed as

Carcinoma, NeuroendocrineMultiple Endocrine Neoplasia Type 2aProto-Oncogene Proteins c-retThyroid NeoplasmsAdolescentAdultFemaleGerm-Line MutationHumansMaleMiddle AgedMosaicismPedigreePolymorphism, Single NucleotidePrevalenceYoung AdultProto-Oncogene Proteins c-retRET protein, humande novo mutationsMEN2MTCRET

Identifiers

PMID40128946
PMCPMC12527454

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.