{"doi":"10.1002/ajmg.a.64233","title":"Case Series of Nizon‐Isidor Syndrome by Heterozygous Variants in <i>MED12L</i> With Further Evidence of Mitotic Instability in One Case With Diploid–Triploid Mosaicism","abstract":"Nizon-Isidor syndrome is a rare disorder caused by heterozygous variants in MED12L, with only eight documented cases in the literature. Here, we present three additional cases of this syndrome. Proband 1 was a 7-year-old female who presented with developmental delay, right-leg hemihypertrophy, laryngeal cleft, esotropia, abnormal skin pigmentation, sectoral iris hypopigmentation, dysphagia, periventricular nodular heterotopia, seizures, morbid obesity, and a pelvic kidney. Genome sequencing (GS) revealed a MED12L variant, NM_053002.5:c.3559+2T>G. Both computational models and transcriptomic analysis confirmed that this variant induced splice loss of MED12L exon 25. Probands 2 and 3 presented with overlapping phenotypes of developmental delay; sequencing confirmed c.3441_3444dup; p.(G1149Nfs*13) and seq[GRCh37] del(3)(q25.1q25.1) chr3:g.?_151075120 variants affecting MED12L. Further investigation found diploid-triploid mosaicism in Proband 1, supporting the hypothesis that loss of MED12L function may increase risk for other cytogenetic abnormalities. Probands 2 and 3 did not harbor evidence of additional cytogenetic aberrations. In Proband 1, caloric restriction and semaglutide-pramlintide combination therapy were started at age eight and were effective in weight reduction. Overall, this report expands the phenotypic spectrum of Nizon-Isidor syndrome, highlights a potential link between MED12L and cytogenetic abnormalities, and demonstrates a case of weight loss through GLP-1 therapy in a child with a genetic obesity syndrome.","journal":"American Journal of Medical Genetics Part A","year":2025,"id":546252,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9383,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1052127,"name":"Kimberly Ezell","orcid":"0009-0005-7200-7644","position":1,"is_corresponding":false},{"id":1437999,"name":"Deanna S. 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