{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:26:09Z","timestamp":1771028769017,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T00:00:00Z","timestamp":1685059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>CHARGE syndrome, due to <jats:italic>CHD7<\/jats:italic> pathogenic variations, is an autosomal dominant disorder characterized by a large spectrum of severity. Despite the great number of variations reported, no clear genotype\u2010to\u2010phenotype correlation has been reported. Unsupervised machine learning and clustering was undertaken using a retrospective cohort of 42 patients, after deep radiologic and clinical phenotyping, to establish genotype\u2013phenotype correlation for <jats:italic>CHD7<\/jats:italic>\u2010related CHARGE syndrome. It resulted in three clusters showing phenotypes of different severities. While no clear genotype\u2013phenotype correlation appeared within the first two clusters, a single patient was outlying the cohort data (cluster 3) with the most atypical phenotype and the most distal frameshift variant in the gene. We added two other patients with similar distal pathogenic variants and observed a tendency toward mild and\/or atypical phenotypes. We hypothesized that this finding could potentially be related to escaping nonsense mediated RNA decay, but found no evidence of such decay in vivo for any of the <jats:italic>CHD7<\/jats:italic> pathogenic variation tested. This indicates that this milder phenotype may rather result from the production of a protein retaining all functional domains.<\/jats:p>","DOI":"10.1111\/cge.14363","type":"journal-article","created":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T06:09:47Z","timestamp":1685167787000},"page":"466-471","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Investigating genotype\u2010to\u2010phenotype correlation in <scp>CHARGE<\/scp> syndrome by deep phenotyping and multiparametric clustering"],"prefix":"10.1111","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0352-4128","authenticated-orcid":false,"given":"J\u00e9r\u00e9my","family":"Dana","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 Institut Imagine, Inserm U1163  Paris France"},{"name":"Service de Radiologie P\u00e9diatrique, AP\u2010HP, H\u00f4pital Necker Enfants Malades Universit\u00e9 Paris cite  Paris 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