{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:48:26Z","timestamp":1790286506738,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The phenotypic variability associated with pathogenic variants in <jats:italic>Lysine Acetyltransferase 6B<\/jats:italic> (<jats:italic>KAT6B<\/jats:italic>, a.k.a. <jats:italic>MORF<\/jats:italic>, <jats:italic>MYST4<\/jats:italic>) results in several interrelated syndromes including Say\u2010Barber\u2010Biesecker\u2010Young\u2010Simpson Syndrome and Genitopatellar Syndrome. Here we present 20 new cases representing 10 novel <jats:italic>KAT6B<\/jats:italic> variants. These patients exhibit a range of clinical phenotypes including intellectual disability, mobility and language difficulties, craniofacial dysmorphology, and skeletal anomalies. Given the range of features previously described for <jats:italic>KAT6B<\/jats:italic>\u2010related syndromes, we have identified additional phenotypes including concern for keratoconus, sensitivity to light or noise, recurring infections, and fractures in greater numbers than previously reported. We surveyed clinicians to qualitatively assess the ways families engage with genetic counselors upon diagnosis. We found that 56% (10\/18) of individuals receive diagnoses before the age of 2\u00a0years (median age\u00a0=\u00a01.96\u00a0years), making it challenging to address future complications with limited accessible information and vast phenotypic severity. We used CRISPR to introduce truncating variants into the <jats:italic>KAT6B<\/jats:italic> gene in model cell lines and performed chromatin accessibility and transcriptome sequencing to identify key dysregulated pathways. This study expands the clinical spectrum and addresses the challenges to management and genetic counseling for patients with <jats:italic>KAT6B<\/jats:italic>\u2010related disorders.<\/jats:p>","DOI":"10.1002\/mgg3.1809","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T10:08:11Z","timestamp":1631614091000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Novel variants in <i>KAT6B<\/i> spectrum of disorders expand our knowledge of clinical manifestations and molecular mechanisms"],"prefix":"10.1002","volume":"9","author":[{"given":"Megan","family":"Yabumoto","sequence":"first","affiliation":[{"name":"Department of Human Genetics David Geffen School of Medicine UCLA Los Angeles California USA"},{"name":"Department of Pathology and Laboratory Medicine David Geffen School of Medicine UCLA Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Kianmahd","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Department of Pediatrics David Geffen School of Medicine UCLA Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghna","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Human Genetics David Geffen School of Medicine UCLA Los Angeles California USA"},{"name":"Department of Pathology and Laboratory Medicine David Geffen School of Medicine UCLA Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria F.","family":"Palafox","sequence":"additional","affiliation":[{"name":"Department of Human Genetics David Geffen School of Medicine UCLA Los Angeles California USA"},{"name":"Department of Pathology and Laboratory Medicine David Geffen School of Medicine UCLA Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine David Geffen School of Medicine UCLA Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Elliott","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine David Geffen School of Medicine UCLA Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana H.","family":"Goodloe","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Alabama at Birmingham Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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