{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T13:04:10Z","timestamp":1780923850511,"version":"3.54.1"},"reference-count":11,"publisher":"BMJ","issue":"1","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2025,9,22]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Pathogenic gain-of-function or dominant-negative effect missense variations in\n                      <jats:italic>ACTB<\/jats:italic>\n                      are associated with a neurodevelopmental disorder characterised by intellectual disability (ID), seizures, sensorineural hearing loss, cerebral, renal and ocular abnormalities and dysmorphic features (Baraitser-Winter cerebrofrontofacial syndrome).\n                      <jats:italic>ACTB<\/jats:italic>\n                      encodes beta-actin, a highly conserved protein involved in cell motility, structure and integrity. Deletions including\n                      <jats:italic>ACTB,<\/jats:italic>\n                      and, more rarely, single-nucleotide loss-of-function variants in\n                      <jats:italic>ACTB<\/jats:italic>\n                      have been described in patients with a distinct phenotype including developmental delay, ID, microcephaly, growth restriction, cardiac and renal abnormalities and dysmorphic features.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We collected 14 individuals and 1 fetus carrying a heterozygous deletion including\n                      <jats:italic>ACTB<\/jats:italic>\n                      , and 4 individuals with a heterozygous truncating variant. Genotypic and phenotypic data were analysed. Furthermore, a comprehensive review of all cases reported to date was also undertaken.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twelve out of 17 individuals presented with ID, and 3 out of 17 with learning disabilities. Speech delay and behavioural abnormalities were observed in 15 out of 17 and 12 out of 17 individuals, respectively, motor delay in 9 out of 17 and growth restriction in 9 out of 18. Most of the individuals (13\/18) had recognisable dysmorphic features. 11 anomalies were de novo, except for 1 deletion inherited from the mother. The size of the deletion varied from 125\u2009kb to 1.6\u2009Mb and could result from a fork stalling and template switching.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study allowed us to better characterise the phenotype associated with the haploinsufficiency of\n                      <jats:italic>ACTB,<\/jats:italic>\n                      underlying the high prevalence of neurodevelopmental disorders (ID, speech and motor delay, behavioural abnormalities) and growth restriction in this recognisable syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmg-2025-110631","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T17:20:36Z","timestamp":1759944036000},"page":"10-14","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["<i>ACTB<\/i>\n                    deletions or single-nucleotide loss-of-function variants: expansion and further delineation of the phenotype and review of the literature"],"prefix":"10.1136","volume":"63","author":[{"given":"Marion","family":"Lesieur-Sebellin","sequence":"first","affiliation":[{"name":"F\u00e9d\u00e9ration de G\u00e9n\u00e9tique et M\u00e9decine G\u00e9nomique, Service de M\u00e9decine G\u00e9nomique des Maladies Rares, APHP.Centre, H\u00f4pital Necker-Enfants Malades, Paris, France"},{"name":"G\u00e9n\u00e9tique des Troubles du Neurod\u00e9veloppement INSERM UMR_1163, Institut Imagine, Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Wigby","sequence":"additional","affiliation":[{"name":"Department of Genetics, Division of Genomic Medicine, UC Davis MIND Institute, Sacramento, California, USA"},{"name":"Rady Children\u2019s Institute for Genomic Medicine, San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, Institut de G\u00e9n\u00e9tique M\u00e9dicale d\u2019Alsace, H\u00f4pitaux Universitaires de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Gouronc","sequence":"additional","affiliation":[{"name":"Laboratoire de diagnostic g\u00e9n\u00e9tique, H\u00f4pitaux Universitaires de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Chatron","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, Hospices Civils de Lyon, Bron Cedex, France"},{"name":"Laboratoire Physiopathologie et G\u00e9n\u00e9tique du Neurone et du Muscle, CNRS UMR 5261, Institut NeuroMyoG\u00e8ne, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Lise","family":"Poulat","sequence":"additional","affiliation":[{"name":"9Service de Neurop\u00e9diatrie, Hospices Civils de Lyon, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Putoux","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, Hospices Civils de Lyon, Lyon, France"},{"name":"INSERM U1028, CNRS UMR5292, UCBL1, GENDEV Team, Neurosciences Research Center of Lyon, Lyon, 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Baraitser-winter cerebrofrontofacial syndrome. In: Adam MP , Feldman J , Mirzaa GM , et al , eds. GeneReviews\u00ae. University of Washington: Seattle, 1993. Available: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK327153\/"},{"key":"2026060805250927000_63.1.10.3","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.95"},{"key":"2026060805250927000_63.1.10.4","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-06713-0","article-title":"Variants in exons 5 and 6 of ACTB cause syndromic thrombocytopenia","volume":"9","author":"Latham","year":"2018","journal-title":"Nat Commun"},{"key":"2026060805250927000_63.1.10.5","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.ejmg.2016.09.008","article-title":"7p22.1 microdeletions involving ACTB associated with developmental delay, short stature, and microcephaly","volume":"59","author":"Shimojima","year":"2016","journal-title":"Eur J Med Genet"},{"key":"2026060805250927000_63.1.10.6","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.ejmg.2017.12.008","article-title":"Refinement of the critical 7p22.1 deletion region: Haploinsufficiency of ACTB is the cause of the 7p22.1 microdeletion-related developmental disorders","volume":"61","author":"Palumbo","year":"2018","journal-title":"Eur J Med Genet"},{"key":"2026060805250927000_63.1.10.7","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/humu.23970","article-title":"Further delineation of putative ACTB loss-of-function variants: A 4-patient series","volume":"41","author":"Baumann","year":"2020","journal-title":"Hum Mutat"},{"key":"2026060805250927000_63.1.10.8","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"2026060805250927000_63.1.10.9","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.250"},{"key":"2026060805250927000_63.1.10.10","doi-asserted-by":"crossref","DOI":"10.1186\/1755-8417-1-4","article-title":"Mechanisms for human genomic rearrangements","volume":"1","author":"Gu","year":"2008","journal-title":"Pathogenetics"},{"key":"2026060805250927000_63.1.10.11","doi-asserted-by":"crossref","first-page":"4232","DOI":"10.1093\/brain\/awac049","article-title":"Activating RAC1 variants in the switch II region cause a developmental syndrome and alter neuronal morphology","volume":"145","author":"Banka","year":"2022","journal-title":"Brain (Bacau)"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg-2025-110631","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T12:26:05Z","timestamp":1780921565000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg-2025-110631"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,8]]},"references-count":11,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12,25]]},"published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1136\/jmg-2025-110631"],"URL":"https:\/\/doi.org\/10.1136\/jmg-2025-110631","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,8]]}}}