{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:40:42Z","timestamp":1787020842939,"version":"build-2736575974"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Epigenet"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Beckwith\u2013Wiedemann syndrome (BWS, OMIM # 130650) is an imprinting disorder, associated with overgrowth and increased risk of embryonal tumors. Patients carrying hypomethylation in the\n                    <jats:italic>KCNQ1OT1<\/jats:italic>\n                    :TSS DMR (11p15.5) show MLID (Multilocus Imprinting Disturbance) upon epimutations at other imprinted regions. Few cases of BWS MLID\u2019s mothers with biallelic pathogenetic variants in maternal effect genes, mainly components of the subcortical maternal complex, are reported. We describe two families, one with a history of conception difficulties with a novel homozygous nonsense\n                    <jats:italic>NLRP2<\/jats:italic>\n                    variant and another experiencing 8 miscarriages with a compound heterozygous\n                    <jats:italic>PADI6<\/jats:italic>\n                    variant.\n                  <\/jats:p>","DOI":"10.1186\/s13148-022-01262-2","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T13:05:00Z","timestamp":1647954300000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Germline variants in genes of the subcortical maternal complex and Multilocus Imprinting Disturbance are associated with miscarriage\/infertility or Beckwith\u2013Wiedemann progeny"],"prefix":"10.1186","volume":"14","author":[{"given":"Pierpaola","family":"Tannorella","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Calzari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Daolio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Mainini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Vimercati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Gentilini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiorenza","family":"Soli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Pedrolli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Bonati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Larizza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5893-0193","authenticated-orcid":false,"given":"Silvia","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"1262_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/nrendo.2017.166","volume":"14","author":"F Brioude","year":"2018","unstructured":"Brioude F, Kalish JM, Mussa A, Foster AC, Bliek J, Ferrero GB, et al. Expert consensus document: clinical and molecular diagnosis, screening and management of Beckwith\u2013Wiedemann syndrome: an international consensus statement. Nat Rev Endocrinol. 2018;14:229\u201349.","journal-title":"Nat Rev Endocrinol"},{"key":"1262_CR2","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1093\/humupd\/dmz045","volume":"26","author":"M Elbracht","year":"2020","unstructured":"Elbracht M, Mackay D, Begemann M, Kagan KO, Eggermann T. Disturbed genomic imprinting and its relevance for human reproduction: causes and clinical consequences. Hum Reprod Update. 2020;26:197\u2013213.","journal-title":"Hum Reprod Update"},{"key":"1262_CR3","doi-asserted-by":"publisher","first-page":"gaab43","DOI":"10.1093\/molehr\/gaab043","volume":"27","author":"D Bebbere","year":"2021","unstructured":"Bebbere D, Albertini DF, Coticchio G, Borini A, Ledda S. The subcortical maternal complex: emerging roles and novel perspectives. Mol Hum Reprod. 2021;27:gaab43.","journal-title":"Mol Hum Reprod."},{"key":"1262_CR4","doi-asserted-by":"publisher","first-page":"e1000423","DOI":"10.1371\/journal.pgen.1000423","volume":"5","author":"E Meyer","year":"2009","unstructured":"Meyer E, Lim D, Pasha S, Tee LJ, Rahman F, Yates JRW, et al. Germline mutation in NLRP2 (NALP2) in a familial imprinting disorder (Beckwith\u2013Wiedemann Syndrome). PLoS Genet. 2009;5:e1000423.","journal-title":"PLoS Genet."},{"key":"1262_CR5","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1136\/jmedgenet-2017-105190","volume":"55","author":"M Begemann","year":"2018","unstructured":"Begemann M, Rezwan FI, Beygo J, Docherty LE, Kolarova J, Schroeder C, et al. Maternal variants in NLRP and other maternal effect proteins are associated with multilocus imprinting disturbance in offspring. J Med Genet. 2018;55:497\u2013504.","journal-title":"J Med Genet"},{"key":"1262_CR6","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1186\/s13148-019-0760-8","volume":"11","author":"A Sparago","year":"2019","unstructured":"Sparago A, Verma A, Patricelli MG, Pignata L, Russo S, Calzari L, et al. The phenotypic variations of multi-locus imprinting disturbances associated with maternal-effect variants of NLRP5 range from overt imprinting disorder to apparently healthy phenotype. Clin Epigenetics. 2019;11:190.","journal-title":"Clin Epigenetics"},{"key":"1262_CR7","doi-asserted-by":"publisher","first-page":"8086","DOI":"10.1038\/ncomms9086","volume":"6","author":"LE Docherty","year":"2015","unstructured":"Docherty LE, Rezwan FI, Poole RL, Turner CLS, Kivuva E, Maher ER, et al. Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans. Nat Commun. 2015;6:8086.","journal-title":"Nat Commun"},{"key":"1262_CR8","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1186\/s13148-020-00925-2","volume":"12","author":"MV Cubellis","year":"2020","unstructured":"Cubellis MV, Pignata L, Verma A, Sparago A, Del Prete R, Monticelli M, et al. Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith\u2013Wiedemann syndrome with multi-locus imprinting disturbance. Clin Epigenetics. 2020;12:139.","journal-title":"Clin Epigenetics"},{"key":"1262_CR9","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/s41431-020-00762-0","volume":"29","author":"T Eggermann","year":"2021","unstructured":"Eggermann T, Kadgien G, Begemann M, Elbracht M. Biallelic PADI6 variants cause multilocus imprinting disturbances and miscarriages in the same family. Eur J Hum Genet. 2021;29:575\u201380.","journal-title":"Eur J Hum Genet"},{"key":"1262_CR10","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1016\/j.ajhg.2016.06.024","volume":"99","author":"Y Xu","year":"2016","unstructured":"Xu Y, Shi Y, Fu J, Yu M, Feng R, Sang Q, et al. Mutations in PADI6 cause female infertility characterized by early embryonic arrest. Am J Hum Genet. 2016;99:744\u201352.","journal-title":"Am J Hum Genet"}],"container-title":["Clinical Epigenetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13148-022-01262-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13148-022-01262-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13148-022-01262-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T13:05:04Z","timestamp":1647954304000},"score":1,"resource":{"primary":{"URL":"https:\/\/clinicalepigeneticsjournal.biomedcentral.com\/articles\/10.1186\/s13148-022-01262-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,22]]},"references-count":10,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["1262"],"URL":"https:\/\/doi.org\/10.1186\/s13148-022-01262-2","relation":{},"ISSN":["1868-7075","1868-7083"],"issn-type":[{"value":"1868-7075","type":"print"},{"value":"1868-7083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,22]]},"assertion":[{"value":"11 January 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 March 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Ethics Committee of Istituto Auxologico Italiano, IRCCS (protocol code CE: 2015_05_05_02; 2021_06_22_03).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the patients to publish this paper.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"43"}}