{"doi":"10.1530/eje-18-0778","title":"Germline and somatic mosaicism in a family with multiple endocrine neoplasia type 1 (MEN1) syndrome","abstract":"<jats:sec>\n<jats:title>Context</jats:title>\n<jats:p>Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease caused by mutations in the tumor suppressor gene <jats:italic>MEN1</jats:italic> and can be diagnosed based on clinical, familial and/or genetic criteria. We present a family in which we found both germline and somatic mosaicism for MEN1.</jats:p>\n</jats:sec>\n<jats:sec>\n<jats:title>Family description</jats:title>\n<jats:p>In our proband, we diagnosed MEN1. The mutation was not detected in her parents (DNA extracted from leucocytes). When her brother was found to harbor the same MEN1 mutation as our proband and, around the same time, their father was diagnosed with a neuroendocrine carcinoma, this tumor was investigated for the MEN1 mutation as well. In the histologic biopsy of this tumor, the same MEN1 mutation was detected as previously found in his children. Re-analysis of his blood using multiplex ligation-dependent probe amplification (MLPA) showed a minimal, but consistently decreased signal for the <jats:italic>MEN1</jats:italic>-specific MLPA probes. The deletion was confirmed in his son by high-resolution array analysis. Based on the array data, we concluded that the deletion was limited to the MEN1 gene and that the father had both germline and somatic mosaicism for <jats:italic>MEN1</jats:italic>.</jats:p>\n</jats:sec>\n<jats:sec>\n<jats:title>Conclusions</jats:title>\n<jats:p>To our knowledge, this is the first reported family with combined germline and somatic mosaicism for MEN1. This study illustrates that germline mosaicism is important to consider in apparently sporadic <jats:italic>de novo MEN1</jats:italic> mutations, because of its particular importance for genetic counseling, specifically when evaluating the risk for family members and when considering the possibility of somatic mosaicism in the parent with germline mosaicism.</jats:p>\n</jats:sec>","journal":"European Journal of Endocrinology","year":2019,"id":688979,"datarank":0.5244761342199721,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.0,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":4,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1799939,"name":"Nike M L Stikkelbroeck","orcid":null,"position":1,"is_corresponding":false},{"id":1799940,"name":"Arjen R Mensenkamp","orcid":null,"position":2,"is_corresponding":false},{"id":360998,"name":"Rolph Pfundt","orcid":"0000-0002-0584-4398","position":3,"is_corresponding":false},{"id":1799941,"name":"Rob B van der Luijt","orcid":null,"position":4,"is_corresponding":false},{"id":870545,"name":"Henri J L M Timmers","orcid":null,"position":5,"is_corresponding":false},{"id":1799942,"name":"Ad R M M Hermus","orcid":null,"position":6,"is_corresponding":false},{"id":1799943,"name":"Marlies J E Kempers","orcid":null,"position":7,"is_corresponding":false},{"id":1799938,"name":"Hanneke J B H Beijers","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Germline and somatic mosaicism in a family with multiple endocrine neoplasia type 1 (MEN1) syndrome","abstract":"<jats:sec>\n<jats:title>Context</jats:title>\n<jats:p>Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease caused by mutations in the tumor suppressor gene <jats:italic>MEN1</jats:italic> and can be diagnosed based on clinical, familial and/or genetic criteria. We present a family in which we found both germline and somatic mosaicism for MEN1.</jats:p>\n</jats:sec>\n<jats:sec>\n<jats:title>Family description</jats:title>\n<jats:p>In our proband, we diagnosed MEN1. The mutation was not detected in her parents (DNA extracted from leucocytes). When her brother was found to harbor the same MEN1 mutation as our proband and, around the same time, their father was diagnosed with a neuroendocrine carcinoma, this tumor was investigated for the MEN1 mutation as well. In the histologic biopsy of this tumor, the same MEN1 mutation was detected as previously found in his children. Re-analysis of his blood using multiplex ligation-dependent probe amplification (MLPA) showed a minimal, but consistently decreased signal for the <jats:italic>MEN1</jats:italic>-specific MLPA probes. The deletion was confirmed in his son by high-resolution array analysis. Based on the array data, we concluded that the deletion was limited to the MEN1 gene and that the father had both germline and somatic mosaicism for <jats:italic>MEN1</jats:italic>.</jats:p>\n</jats:sec>\n<jats:sec>\n<jats:title>Conclusions</jats:title>\n<jats:p>To our knowledge, this is the first reported family with combined germline and somatic mosaicism for MEN1. This study illustrates that germline mosaicism is important to consider in apparently sporadic <jats:italic>de novo MEN1</jats:italic> mutations, because of its particular importance for genetic counseling, specifically when evaluating the risk for family members and when considering the possibility of somatic mosaicism in the parent with germline mosaicism.</jats:p>\n</jats:sec>","is_dataset_classified":null,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"datacite_reuse_total":4,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30481156","pmcid":null,"openalex_id":"https://openalex.org/W2902063991","authors":[],"funders":[],"total_grants":0,"fwci":1.9489,"citation_percentile":0.86503878,"influential_citations":0,"citation_trend":[{"year":2020,"count":7},{"year":2021,"count":6},{"year":2022,"count":8},{"year":2023,"count":2},{"year":2024,"count":4},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://eje.bioscientifica.com/view/journals/eje/180/2/EJE-18-0778.xml","host_type":"publisher"},{"url":"https://doi.org/10.1530/eje-18-0778","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30481156","host_type":"repository"},{"url":"http://hdl.handle.net/2066/202908","host_type":"repository"}],"fields_of_study":["Neuroendocrine Tumor Research Advances","Lung Cancer Research Studies","Microtubule and mitosis dynamics","Adult","Female","Germ-Line Mutation","Humans","Male","Mosaicism","Multiple Endocrine Neoplasia Type 1","Pedigree"],"mesh_terms":["Adult","Female","Humans","Male","Mosaicism","Pedigree","Germ-Line Mutation","Multiple Endocrine Neoplasia Type 1"],"keywords":["MEN1","Multiple endocrine neoplasia","Germline mutation","Germline mosaicism","Germline","Proband","Multiplex ligation-dependent probe amplification","Genetics","Biology","Somatic cell","Mutation","Cancer research","Internal medicine","Medicine","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.19320953.v1","title":"Additional file 1 of Multiple endocrine neoplasia type 1: a new germline “homozygous” variant (c.201delC) caused by detection errors","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19320953","title":"Additional file 1 of Multiple endocrine neoplasia type 1: a new germline “homozygous” variant (c.201delC) caused by detection errors","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19320956","title":"Additional file 2 of Multiple endocrine neoplasia type 1: a new germline “homozygous” variant (c.201delC) caused by detection errors","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19320956.v1","title":"Additional file 2 of Multiple endocrine neoplasia type 1: a new germline “homozygous” variant (c.201delC) caused by detection errors","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-19T21:03:11.997179Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}