biostudies-literatureCali EEuropean Research CouncilMichael J Fox Foundation for Parkinson&apos;s ResearchMedical Research CouncilNHGRI NIH HHSUehara Memorial FoundationNINDS NIH HHSNational Institutes of HealthRettsyndrome.orgWellcome TrustNational Human Genome Research InstituteNIGMS NIH HHSMuscular Dystrophy Association101251https://www.ebi.ac.uk/biostudies/studies/S-EPMC12042808biostudies-literatureUnknown27(4)<h4>Purpose</h4>This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.<h4>Methods</h4>We identified 105 affected individuals, including 39 previously reported cases, and systematically analyzed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis.<h4>Results</h4>Biallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability, infantile intractable seizures, absGenetics in medicine : official journal of the American College of Medical GeneticsClinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders.PMC12042808U01 HG011758R35 NS105078R01 GM073791K08 HG008986T32 GM007526WT093205MAHague JSezer OSaadi NWVoinova VStefanich JCarr LAlqarajeh FMansoor SRiva AVissers LELMMaroofian RBeecroft FAnjum MNBauer PElbendary HMCoubes CMoreno-De-Luca AQuirin TAbbaszadegan MRLupski JRStrehlow VJosahkian JMoran ECristian IMarinakis NMMaria de Miranda Henriques-Souza AElias Maia RGowda VKMurphy DKanaan MMorrison JTawde SIbrahim SMilh MZeidler SPappas JJain VMiryounesi MCali EKanani FGleeson JGPosey JEJaved IBispo LZaki MSChatron NJamra RAChalla VSRChung WKBegtrup ALarki PMor-Shaked HAgolini ERyba LAskander OElAwady HAVillard LNovelli AHosseini SGhayoor Karimiani EEfthymiou SMontazer Zohour MVictor LAMacek MIdkaidak SStriano PRocca CSuri MThiffault ILafontaine DLJCanavati CTesner PDominguez REl Fahime EMitani TVille DRana NKitajima JPMarafi DBertsch NLNeshatdoust MMau-Them FTNoh GJKok FAbdelkreem EElmaksoud MATraeger-Synodinos JTay CGChand PHoulden HCampeau PMBruel ALAtawneh OGencpinar PHarel THalbach SSOpperman HPehlivan DFiroozfar ZSrinivasan VMUstun CAbdel-Hamid MSHashemi-Gorji FPinero-Banos BLesca GHerman IIssa MYAlavi SAmor DJZifarelli GZafar FUnay BNeul JLMorsy HEl Khassab HHane LMonteiro FMullegama SVPagnamenta ATKamal LLettori DAlkuraya FSNizon MRashidi-Nezhad ACaumes RVasco GHaider SLevchenko OCheema HAfalseClinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders.<h4>Purpose</h4>This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.<h4>Methods</h4>We identified 105 affected individuals, including 39 previously reported cases, and systematically analyzed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis.<h4>Results</h4>Biallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability, infantile intractable seizures, abs2025-01-01T00:00:00Z2025 Apr2026-06-03T23:17:30.636Z2026-05-03T03:10:13.111ZS-EPMC120428083927594810.1016/j.gim.2024.101251