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Thus, <jats:italic>ZNF445<\/jats:italic> pathogenic variants are predicted to cause multilocus imprinting disturbances (MLIDs), as do <jats:italic>ZFP57<\/jats:italic> pathogenic variants. In particular, the <jats:italic>MEG3\/DLK1<\/jats:italic>:IG-DMR would be affected, because the postzygotic methylation imprint of the <jats:italic>MEG3\/DLK1<\/jats:italic>:IG-DMR is maintained primarily by ZNF445, whereas that of most iDMRs is preserved by both ZFP57 and ZNF445 or primarily by ZFP57.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We searched for a <jats:italic>ZNF445<\/jats:italic> variant(s) in six patients with various imprinting disorders (IDs) caused by epimutations and MLIDs revealed by pyrosequencing for nine iDMRs, without a selection for the original IDs. Re-analysis of the previously obtained whole exome sequencing data identified a homozygous <jats:italic>ZNF445<\/jats:italic> variant (NM_181489.6:c.2803C&gt;T:p.(Gln935*)) producing a truncated protein missing two of 14 zinc finger domains in a patient with Temple syndrome and MLID. In this patient, array-based genomewide methylation analysis revealed severe hypomethylation of most CpGs at the <jats:italic>MEG3<\/jats:italic>:TSS-DMR, moderate hypomethylation of roughly two-thirds of CpGs at the <jats:italic>H19\/IGF2<\/jats:italic>:IG-DMR, and mild-to-moderate hypomethylation of a few CpGs at the <jats:italic>DIRAS3<\/jats:italic>:TSS-DMR, <jats:italic>MEST<\/jats:italic>:alt-TSS-DMR, <jats:italic>IGF2<\/jats:italic>:Ex9-DMR, <jats:italic>IGF2<\/jats:italic>:alt-TSS, and <jats:italic>GNAS<\/jats:italic>-<jats:italic>AS1<\/jats:italic>:TSS-DMR. Furthermore, bisulfite sequencing analysis for the <jats:italic>MEG3\/DLK1<\/jats:italic>:IG-DMR delineated a markedly hypomethylated segment (CG-A). The heterozygous parents were clinically normal and had virtually no aberrant methylation pattern.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We identified a <jats:italic>ZNF445<\/jats:italic> pathogenic variant for the first time. Since ZNF445 binds to the <jats:italic>MEG3\/DLK1<\/jats:italic>:IG-DMR and other iDMRs affected in this patient, the development of Temple syndrome and MLID would primarily be explained by the <jats:italic>ZNF445<\/jats:italic> variant. Furthermore, CG-A may be the target site for ZNF445 within the <jats:italic>MEG3\/DLK1<\/jats:italic>:IG-DMR.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13148-021-01106-5","type":"journal-article","created":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T20:03:20Z","timestamp":1622059400000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["ZNF445: a homozygous truncating variant in a patient with Temple syndrome and multilocus imprinting disturbance"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3020-455X","authenticated-orcid":false,"given":"Masayo","family":"Kagami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Hara-Isono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Matsubara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Nakabayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Narumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Fukami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumiko","family":"Ohkubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotomo","family":"Saitsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Takada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Ogata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,26]]},"reference":[{"key":"1106_CR1","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1515\/bmc-2014-0037","volume":"6","author":"DJ Mackay","year":"2015","unstructured":"Mackay DJ, Eggermann T, Buiting K, Garin I, Netchine I, Linglart A, et al. 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