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The variability in syndromic presentation between patients may be partially explained by variants in chromatin regulatory genes that act to further modify TBX1 function. To investigate this relationship, we selected\n                    <jats:italic>KMT2D<\/jats:italic>\n                    as a candidate gene because of its role in the etiology of Kabuki syndrome, which shares overlapping features with 22q11.2DS. We demonstrate that conditional inactivation of\n                    <jats:italic>Kmt2d<\/jats:italic>\n                    in the\n                    <jats:italic>Tbx1<\/jats:italic>\n                    lineage in\n                    <jats:italic>Tbx1<\/jats:italic>\n                    -heterozygous mice leads to fully penetrant perinatal lethality and increased incidence of craniofacial dysmorphism, thymus and parathyroid gland hypoplasia, and aortic arch anomalies. At early stages, mutant embryos were found to have defects of the caudal pharyngeal apparatus, including abnormal patterning of the third pouch endoderm, hypoplastic fourth arches, and defective fourth arch arteries. Finally, analysis of single-cell RNA sequencing revealed dysregulation, and largely downregulation, of genes involved in basic cellular functions, suggesting that\n                    <jats:italic>Tbx1<\/jats:italic>\n                    and\n                    <jats:italic>Kmt2d<\/jats:italic>\n                    developmentally converge upon essential biological processes. Overall, these results indicate that reduced dosage of\n                    <jats:italic>Kmt2d<\/jats:italic>\n                    perturbs the developmental landscape of the\n                    <jats:italic>Tbx1<\/jats:italic>\n                    heterozygote, eliciting phenotypes that are shared between 22q11.2DS and Kabuki syndrome.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.206763","type":"journal-article","created":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:01:06Z","timestamp":1787508066000},"source":"Crossref","is-referenced-by-count":0,"title":["Reduced dosage of Kmt2d modifies Tbx1 haploinsufficiency toward phenotypes of 22q11.2DS"],"prefix":"10.1172","volume":"11","author":[{"given":"Daniella","family":"Miller","sequence":"first","affiliation":[{"name":"Department of Genetics, Department of Obstetrics & Gynecology and Women\u2019s Health, and Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, 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