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Here we describe a new neurodevelopmental disorder associated with variants in <jats:italic>ZBTB47<\/jats:italic> (also known as <jats:italic>ZNF651<\/jats:italic>), which encodes zinc finger and BTB domain\u2010containing protein 47. Exome sequencing (ES) was performed for five unrelated patients with neurodevelopmental disorders. All five patients are heterozygous for a de novo missense variant in <jats:italic>ZBTB47<\/jats:italic>, with p.(Glu680Gly) (c.2039A&gt;G) detected in one patient and p.(Glu477Lys) (c.1429G&gt;A) identified in the other four patients. Both variants impact conserved amino acid residues. Bioinformatic analysis of each variant is consistent with pathogenicity. We present five unrelated patients with de novo missense variants in <jats:italic>ZBTB47<\/jats:italic> and a phenotype characterized by developmental delay with intellectual disability, seizures, hypotonia, gait abnormalities, and variable movement abnormalities. We propose that these variants in <jats:italic>ZBTB47<\/jats:italic> are the basis of a new neurodevelopmental disorder.<\/jats:p>","DOI":"10.1002\/ajmg.a.63399","type":"journal-article","created":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T07:35:23Z","timestamp":1695627323000},"page":"17-30","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["De novo missense variants in <i>ZBTB47<\/i> are associated with developmental delays, hypotonia, seizures, gait abnormalities, and variable movement abnormalities"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6052-1900","authenticated-orcid":false,"given":"Scott K.","family":"Ward","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine (BCM)  Houston Texas USA"},{"name":"Department of Pediatrics, Division of Medical Genetics and Genomic Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandrea","family":"Wadley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Genetics University of Oklahoma Health Sciences Center  Oklahoma City Oklahoma USA"},{"name":"University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun\u2010hui (Anne)","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Genetics University of Oklahoma Health Sciences Center  Oklahoma City Oklahoma USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Benke","sequence":"additional","affiliation":[{"name":"Joe DiMaggio Children's Hospital  Hollywood Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Emrick","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Neurology and Developmental Neuroscience Baylor College of Medicine (BCM)  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Neurology and Developmental Neuroscience Baylor College of Medicine (BCM)  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly M.","family":"Houck","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Neurology and Developmental Neuroscience Baylor College of Medicine (BCM)  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongzheng","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine (BCM)  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Undiagnosed Diseases Network","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria J.","family":"Guillen Sacoto","sequence":"additional","affiliation":[{"name":"GeneDx  Gaithersburg Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Craigen","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine (BCM)  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly","family":"Glaser","sequence":"additional","affiliation":[{"name":"Joe DiMaggio Children's Hospital  Hollywood Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Murdock","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine (BCM)  Houston Texas USA"},{"name":"The University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Rohena","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics San Antonio Military Medical Center  San Antonio Texas USA"},{"name":"Department of Pediatrics Long School of Medicine, The University of Texas Health Science Center at San Antonio  San Antonio Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin E. 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