{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:24:13Z","timestamp":1790627053361,"version":"4.1.0"},"reference-count":24,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T00:00:00Z","timestamp":1639353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <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 MEN1. The uncertainty of pathogenicity of MEN1 variants complexifies the selection of the patients likely to benefit from specific care.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>MEN1-mutated patients should be offered tailored tumor screening and genetic counseling. We present a patient with hyperparathyroidism for whom genetic analysis identified a variant of uncertain significance in the MEN1 gene (NM_130799.2): c.654G\u2005&amp;gt;\u2005T p.(Arg218=). Additional functional genetic tests were performed to classify the variant as pathogenic and allowed prenatal testing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Targeted next generation sequencing identified a synonymous variant in the MEN1 gene in a 26-year-old male with symptomatic primary hyperparathyroidism. In silico and in vitro genetic tests were performed to assess variant pathogenicity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Genetic testing of the proband\u2019s unaffected parents showed the variant occurred de novo. Transcript study showed a splicing defect leading to an in-frame deletion. The classification of the MEN1 variant as pathogenic confirmed the diagnosis of MEN1 and recommended an adapted medical care and follow-up. Pathogenic classification also allowed to propose a genetic counseling to the proband and his wife. Noninvasive prenatal diagnosis was performed with a personalized medicine-based protocol by detection of the paternally inherited variant in maternal plasmatic cell free DNA, using digital PCR.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We showed that functional genetic analysis can help to assess the pathogenicity of a MEN1 variant with crucial consequences for medical care and genetic counseling decisions.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgab894","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T13:24:24Z","timestamp":1639401864000},"page":"e1367-e1373","source":"Crossref","is-referenced-by-count":7,"title":["Noninvasive Prenatal Diagnosis of a Paternally Inherited <i>MEN1<\/i> Pathogenic Splicing Variant"],"prefix":"10.1210","volume":"107","author":[{"given":"Thomas","family":"Huby","sequence":"first","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires, H\u00f4pital Cochin, DMU BioPhyGen, Assistance Publique-H\u00f4pitaux de Paris, AP-HP.Centre-Universit\u00e9 de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edouard","family":"Le Guillou","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires, H\u00f4pital Cochin, DMU BioPhyGen, Assistance Publique-H\u00f4pitaux de Paris, AP-HP.Centre-Universit\u00e9 de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril","family":"Burin des Roziers","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires, H\u00f4pital Cochin, DMU BioPhyGen, Assistance Publique-H\u00f4pitaux de Paris, AP-HP.Centre-Universit\u00e9 de Paris, Paris, France"},{"name":"Institut Cochin, Inserm U1016, CNRS UMR8104, Universit\u00e9 de Paris, CARPEM, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Pacot","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires, H\u00f4pital Cochin, DMU BioPhyGen, Assistance Publique-H\u00f4pitaux de Paris, AP-HP.Centre-Universit\u00e9 de Paris, Paris, France"},{"name":"Institut Cochin, Inserm U1016, CNRS UMR8104, Universit\u00e9 de Paris, CARPEM, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Briand-Suleau","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires, H\u00f4pital Cochin, DMU BioPhyGen, Assistance Publique-H\u00f4pitaux de Paris, AP-HP.Centre-Universit\u00e9 de Paris, Paris, France"},{"name":"Institut Cochin, Inserm U1016, CNRS UMR8104, Universit\u00e9 de Paris, CARPEM, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albain","family":"Chansavang","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires, H\u00f4pital Cochin, DMU BioPhyGen, Assistance Publique-H\u00f4pitaux de Paris, AP-HP.Centre-Universit\u00e9 de Paris, Paris, France"},{"name":"Institut Cochin, Inserm U1016, CNRS UMR8104, Universit\u00e9 de Paris, CARPEM, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Toussaint","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires, H\u00f4pital Cochin, DMU BioPhyGen, Assistance Publique-H\u00f4pitaux de Paris, AP-HP.Centre-Universit\u00e9 de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Duchossoy","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires, H\u00f4pital Cochin, DMU BioPhyGen, Assistance Publique-H\u00f4pitaux de Paris, AP-HP.Centre-Universit\u00e9 de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Vaucouleur","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires, H\u00f4pital Cochin, DMU BioPhyGen, Assistance Publique-H\u00f4pitaux de Paris, AP-HP.Centre-Universit\u00e9 de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Benoit","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires, H\u00f4pital Cochin, DMU BioPhyGen, Assistance Publique-H\u00f4pitaux de Paris, AP-HP.Centre-Universit\u00e9 de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Lod\u00e9","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires, H\u00f4pital Cochin, DMU BioPhyGen, Assistance Publique-H\u00f4pitaux de Paris, AP-HP.Centre-Universit\u00e9 de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9mence","family":"Molac","sequence":"additional","affiliation":[{"name":"Maternit\u00e9 Port-Royal, FHU PREMA, AP-HP, H\u00f4pital Cochin, AP-HP.Centre-Universit\u00e9 de Paris, Universit\u00e9 de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Odile","family":"North","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires, H\u00f4pital Cochin, DMU BioPhyGen, Assistance Publique-H\u00f4pitaux de Paris, AP-HP.Centre-Universit\u00e9 de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Grotto","sequence":"additional","affiliation":[{"name":"Maternit\u00e9 Port-Royal, FHU PREMA, AP-HP, H\u00f4pital Cochin, AP-HP.Centre-Universit\u00e9 de Paris, Universit\u00e9 de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7650-6660","authenticated-orcid":false,"given":"Vassilis","family":"Tsatsaris","sequence":"additional","affiliation":[{"name":"Maternit\u00e9 Port-Royal, FHU PREMA, AP-HP, H\u00f4pital Cochin, AP-HP.Centre-Universit\u00e9 de Paris, Universit\u00e9 de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Jouinot","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, H\u00f4pital Cochin, AP-HP.Centre-Universit\u00e9 de Paris, Universit\u00e9 de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9atrix","family":"Cochand-Priollet","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cochin Hospital, AP-HP.Centre-Universit\u00e9 de Paris, Universit\u00e9 de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-C\u00e9cile","family":"Paepegaey","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, M\u00e9dip\u00f4le H\u00f4pital Mutualiste, Villeurbanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Nectoux","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires, H\u00f4pital Cochin, DMU BioPhyGen, Assistance Publique-H\u00f4pitaux de Paris, AP-HP.Centre-Universit\u00e9 de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Groussin","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, H\u00f4pital Cochin, AP-HP.Centre-Universit\u00e9 de Paris, Universit\u00e9 de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1881-8762","authenticated-orcid":false,"given":"Eric","family":"Pasmant","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires, H\u00f4pital Cochin, DMU BioPhyGen, Assistance Publique-H\u00f4pitaux de Paris, AP-HP.Centre-Universit\u00e9 de Paris, Paris, France"},{"name":"Institut Cochin, Inserm U1016, CNRS UMR8104, Universit\u00e9 de Paris, CARPEM, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,12,13]]},"reference":[{"issue":"4","key":"2022032516105880800_CIT0001","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41574-021-00468-3","article-title":"Clinical aspects of multiple endocrine neoplasia type 1","volume":"17","author":"Al-Salameh","year":"2021","journal-title":"Nat Rev 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