biostudies-literatureWeiss KIntramural NIH HHSNHLBI NIH HHSNational Institute for Health Research (NIHR)Wellcome TrustNIH HHS389-397https://www.ebi.ac.uk/biostudies/studies/S-EPMC8900827biostudies-literatureUnknown22(2)<h4>Purpose</h4>Sifrim-Hitz-Weiss syndrome (SIHIWES) is a recently described multisystemic neurodevelopmental disorder caused by de novo variants inCHD4. In this study, we investigated the clinical spectrum of the disorder, genotype-phenotype correlations, and the effect of different missense variants on CHD4 function.<h4>Methods</h4>We collected clinical and molecular data from 32 individuals with mostly de novo variants in CHD4, identified through next-generation sequencing. We performed adenosine triphosphate (ATP) hydrolysis and nucleosome remodeling assays on variants from five different CHD4 domains.<h4>Results</h4>The majority of participants had global developmental delay, mild to moderate intellectual disability, brain anomalies, congenital heart defects, and dysmorphic features. Genetics in medicine : official journal of the American College of Medical GeneticsThe CHD4-related syndrome: a comprehensive investigation of the clinical spectrum, genotype-phenotype correlations, and molecular basis.PMC8900827UM1 HL172717UM1 HL128711UM1 HL098147S10 OD026880Z01 ES101965UM1 HL098123HICF-1009-003U01 HL131003ZIA ES101965WT098051UM1 HL128761UM1 HL098162Keren BClayton-Smith JMedne LQuinonez SCTakaku MTerhal PWright MZackai EHGhoumid JHove HRoeder ERKurolap AKrock BPetrovich RMRumple MKurumizaka HSmol TLazar HPCampeau PMColin ESantani AJain MDubbs HAGambello MNugent Kvan Haeringen ASkraban CMParker MJWade PAMonteil DTurnpenny PGelb BDSchrier Vergano SAMartinez AFLachlan KWhalen SZiegler ASmeland MFKenney APaperna TWeiss KDeChene ECohen LHeide SIrving MRoberts JDMetcalfe KBaris Feldman HMuenke MfalseThe CHD4-related syndrome: a comprehensive investigation of the clinical spectrum, genotype-phenotype correlations, and molecular basis.<h4>Purpose</h4>Sifrim-Hitz-Weiss syndrome (SIHIWES) is a recently described multisystemic neurodevelopmental disorder caused by de novo variants inCHD4. In this study, we investigated the clinical spectrum of the disorder, genotype-phenotype correlations, and the effect of different missense variants on CHD4 function.<h4>Methods</h4>We collected clinical and molecular data from 32 individuals with mostly de novo variants in CHD4, identified through next-generation sequencing. We performed adenosine triphosphate (ATP) hydrolysis and nucleosome remodeling assays on variants from five different CHD4 domains.<h4>Results</h4>The majority of participants had global developmental delay, mild to moderate intellectual disability, brain anomalies, congenital heart defects, and dysmorphic features. 2020-01-01T00:00:00Z2020 Feb2026-05-31T02:02:06.905Z2024-11-09T08:03:34.374ZS-EPMC89008273138819010.1038/s41436-019-0612-0