{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T10:43:09Z","timestamp":1766486589584,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T00:00:00Z","timestamp":1684108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Rare Diseases: Models &amp; Mechanisms (RDMM), Canadian Institutes of Health Research (CIHR)"},{"name":"Dalhousie Medical School summer research funding"},{"name":"IWK Health Centre Doctoral Award"},{"name":"CIHR post-doctoral award"},{"name":"CHARGE Syndrome Foundation"},{"name":"Texas Chargers"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>CHARGE syndrome typically results from mutations in the gene encoding chromodomain helicase DNA-binding protein 7 (CHD7). CHD7 is involved in regulating neural crest development, which gives rise to tissues of the skull\/face and the autonomic nervous system (ANS). Individuals with CHARGE syndrome are frequently born with anomalies requiring multiple surgeries and often experience adverse events post-anesthesia, including oxygen desaturations, decreased respiratory rates, and heart rate abnormalities. Central congenital hypoventilation syndrome (CCHS) affects ANS components that regulate breathing. Its hallmark feature is hypoventilation during sleep, clinically resembling observations in anesthetized CHARGE patients. Loss of PHOX2B (paired-like homeobox 2b) underlies CCHS. Employing a chd7-null zebrafish model, we investigated physiologic responses to anesthesia and compared these to loss of phox2b. Heart rates were lower in chd7 mutants compared to the wild-type. Exposure to tricaine, a zebrafish anesthetic\/muscle relaxant, revealed that chd7 mutants took longer to become anesthetized, with higher respiratory rates during recovery. chd7 mutant larvae demonstrated unique phox2ba expression patterns. The knockdown of phox2ba reduced larval heart rates similar to chd7 mutants. chd7 mutant fish are a valuable preclinical model to investigate anesthesia in CHARGE syndrome and reveal a novel functional link between CHARGE syndrome and CCHS.<\/jats:p>","DOI":"10.3390\/genes14051086","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T02:56:57Z","timestamp":1684119417000},"page":"1086","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["phox2ba: The Potential Genetic Link behind the Overlap in the Symptomatology between CHARGE and Central Congenital Hypoventilation Syndromes"],"prefix":"10.3390","volume":"14","author":[{"given":"Jessica E.","family":"MacLean","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Dalhousie University, Halifax, NS B3K 6R8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6029-3376","authenticated-orcid":false,"given":"Jaime N.","family":"Wertman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey V.","family":"Prykhozhij","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Chedrawe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dalhousie University, Halifax, NS B3K 6R8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stewart","family":"Langley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dalhousie University, Halifax, NS B3K 6R8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelby L.","family":"Steele","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dalhousie University, Halifax, NS B3K 6R8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Ban","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4234-3230","authenticated-orcid":false,"given":"Kim","family":"Blake","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dalhousie University, Halifax, NS B3K 6R8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4053-6067","authenticated-orcid":false,"given":"Jason N.","family":"Berman","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada"},{"name":"Departments of Pediatrics and Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0022-3476(81)80454-4","article-title":"Coloboma, Congenital Heart Disease, and Choanal Atresia with Multiple Anomalies: CHARGE Association","volume":"99","author":"Pagon","year":"1981","journal-title":"J Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1002\/humu.22086","article-title":"Mutation Update on the CHD7 Gene Involved in CHARGE Syndrome","volume":"33","author":"Janssen","year":"2012","journal-title":"Hum. 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