{"id":1061,"date":"2025-10-08T16:00:14","date_gmt":"2025-10-08T16:00:14","guid":{"rendered":"http:\/\/sebigec.es\/blog\/?guid=eb8f8f99da7a68793d365644f0a3bf86"},"modified":"2025-12-26T05:51:05","modified_gmt":"2025-12-26T05:51:05","slug":"actb-deletions-or-single-nucleotide-loss-of-function-variants-expansion-and-further-delineation-of-the-phenotype-and-review-of-the-literature","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2025\/10\/08\/actb-deletions-or-single-nucleotide-loss-of-function-variants-expansion-and-further-delineation-of-the-phenotype-and-review-of-the-literature\/","title":{"rendered":"ACTB deletions or single-nucleotide loss-of-function variants: expansion and further delineation of the phenotype and review of the literature"},"content":{"rendered":"\n<sec><st>Background<\/st>\n<p>Pathogenic gain-of-function or dominant-negative effect missense variations in <I>ACTB<\/I> 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). <I>ACTB<\/I> encodes beta-actin, a highly conserved protein involved in cell motility, structure and integrity. Deletions including <I>ACTB,<\/I> and, more rarely, single-nucleotide loss-of-function variants in <I>ACTB<\/I> have been described in patients with a distinct phenotype including developmental delay, ID, microcephaly, growth restriction, cardiac and renal abnormalities and dysmorphic features.<\/p>\n<\/sec>\n<sec><st>Methods<\/st>\n<p>We collected 14 individuals and 1 fetus carrying a heterozygous deletion including <I>ACTB<\/I>, 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.<\/p>\n<\/sec>\n<sec><st>Results<\/st>\n<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 kb to 1.6 Mb and could result from a fork stalling and template switching.<\/p>\n<\/sec>\n<sec><st>Conclusion<\/st>\n<p>This study allowed us to better characterise the phenotype associated with the haploinsufficiency of <I>ACTB,<\/I> underlying the high prevalence of neurodevelopmental disorders (ID, speech and motor delay, behavioural abnormalities) and growth restriction in this recognisable syndrome.<\/p>\n<\/sec>\n","protected":false},"excerpt":{"rendered":"<p>Background<br \/>\nPathogenic gain-of-function or dominant-negative effect missense variations in ACTB are associated with a neurodevelopmental disorder characterised by intellectual disability (ID), seizures, sensorineural hearing loss, cerebral, renal and o&#8230;<\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,14],"tags":[83],"class_list":["post-1061","post","type-post","status-publish","format-standard","hentry","category-articulos","category-jmg","tag-jmedgenet"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/1061","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=1061"}],"version-history":[{"count":3,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/1061\/revisions"}],"predecessor-version":[{"id":4742,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/1061\/revisions\/4742"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=1061"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=1061"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=1061"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}