Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals

Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants in the two genes that encode histone H3.3 (H3-3A/H3F3A and H3-3B/H3F3B) [1-4]. This syndrome is characterized by developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, and abnormal neuroimaging [1, 5]. BLBS was initially categorized as a progressive neurodegenerative syndrome caused by de novo heterozygous variants in either H3-3A or H3-3B [1-4]. Here, we analyze the data of the 58 previously published individuals along 38 unpublished, unrelated individuals. In this larger cohort of 96 people, we identify causative missense, synonymous, and stop-loss variants. We also expand upon the phenotypic characterization by elaborating on the neurodevelopmental component of BLBS. Notably, phenotypic heterogeneity was present even amongst individuals harboring the same variant. To explore the complex phenotypic variation in this expanded cohort, the relationships between syndromic phenotypes with three variables of interest were interrogated: sex, gene containing the causative variant, and variant location in the H3.3 protein. While specific genotype-phenotype correlations have not been conclusively delineated, the results presented here suggest that the location of the variants within the H3.3 protein and the affected gene (H3-3A or H3-3B) contribute more to the severity of distinct phenotypes than sex. Since these variables do not account for all BLBS phenotypic variability, these findings suggest that additional factors may play a role in modifying the phenotypes of affected individuals. Histones are poised at the interface of genetics and epigenetics, highlighting the potential role for gene-environment interactions and the importance of future research

Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals

Espectro fenotípico; Síndrome de Bryant-Li-Bhoj; Trastorno neurodegenerativoEspectre fenotípic; Síndrome de Bryant-Li-Bhoj; Trastorn neurodegeneratiuPhenotypic spectrum; Bryant-Li-Bhoj syndrome; Neurodegenerative disorderBryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants in the two genes that encode histone H3.3 (H3-3A/H3F3A and H3-3B/H3F3B) [1–4]. This syndrome is characterized by developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, and abnormal neuroimaging [1, 5]. BLBS was initially categorized as a progressive neurodegenerative syndrome caused by de novo heterozygous variants in either H3-3A or H3-3B [1–4]. Here, we analyze the data of the 58 previously published individuals along 38 unpublished, unrelated individuals. In this larger cohort of 96 people, we identify causative missense, synonymous, and stop-loss variants. We also expand upon the phenotypic characterization by elaborating on the neurodevelopmental component of BLBS. Notably, phenotypic heterogeneity was present even amongst individuals harboring the same variant. To explore the complex phenotypic variation in this expanded cohort, the relationships between syndromic phenotypes with three variables of interest were interrogated: sex, gene containing the causative variant, and variant location in the H3.3 protein. While specific genotype-phenotype correlations have not been conclusively delineated, the results presented here suggest that the location of the variants within the H3.3 protein and the affected gene (H3-3A or H3-3B) contribute more to the severity of distinct phenotypes than sex. Since these variables do not account for all BLBS phenotypic variability, these findings suggest that additional factors may play a role in modifying the phenotypes of affected individuals. Histones are poised at the interface of genetics and epigenetics, highlighting the potential role for gene-environment interactions and the importance of future research.This study was supported by NHGRI T32 5T32HG009495 and the Eagles Autism Foundation (DELC), NICHD F30 1F30HD112125 (EEL), NIGMS T32GM008638 (LMB, ELD), NICHD P50HD109879 (WKC), NU22-07-00165 (MH, SB, DP, AB). Additionally, this was funded by Burroughs Wellcome Fund, Hartwell Foundation, and the Chan Zuckerberg Initiative (EJKB)

Structural Stability

IASS-IACM 2008 Session: Structural Stability -- Session Organizer: Herbert MANG (Technical University of Vienna) -- Plenary Lecture: Abstract, Slides and Video: "Answers to three not quite straightforward questions in structural stability" by Andreas STEINBOECK, Gerhard HOEFINGER, Xin JIA, Herbert A. MANG (Technical University of Vienna) -- Keynote Lecture: "Limit-point and postbuckling behavior of steel trusses under thermal and mechanical loadings" by Yeong Bin YANG , T.J. LIN (National Taiwan University) -- "Modeling thin-walled cold-formed steel members and systems" by Benjamin W. SCHAFER , R. H. SANGREE, Cristopher MOEN, M. SEIF, Y. SHIFFERAW, V. ZEINODDINI, Z. J. LI, O. IUORIO, Y. GUAN (Johns Hopkins University) -- "Multi parametrical instability of straight bars" by Jan B. OBREBSKI (Warsaw University of Technology) -- "The effect of predetermined delaminations on buckling and post-buckling behavior of spatial composite timber beams and frames" by Miran SAJE , Urban RODMAN, Dejan ZUPAN, Igor PLANINC (University of Ljubljana) -- Keynote Lecture: "Buckling and sensitivity analysis of imperfect shells involving contact" by Karl SCHWEIZERHOF , Eduard EWERT (University of Karlsruhe) -- Keynote Lecture: "Determining the stability of tensegrities and generic global rigidity" by Robert CONNELLY (Cornell University) -- "Initial imperfection identification in shell buckling problems" by Christopher J. STULL , Christopher J. EARLS, Wilkins AQUINO (Cornell University) -- "Buckling phenomena, analysis and design of axially compressed cylindrical shells with co-existent external pressure" by Werner GUGGENBERGER , Medhanye B. TEKLEAB (TU Graz

Stop-Splayed Scarf-Joint Reinforcement with Timber Pegs Behaviour

Restoring ancient timber structures often involves cutting or reinforcing stop-splayed scarf-joints in beams or truss-rods. Steel nails, bolts and plates or adhesive resins and rods are commonly used, however these jointing technologies cause some disadvantages, such as moisture between steel and timber surfaces, hard reversibility of the intervention and a questionable aesthetic output in uncovered structures. The employment of timber pegs, inserted perpendicular to the grain, could be an efficient solution and is already preferred in some applications. Since no design rules for traditional timber joints or for timber pegged connections are given by European codes, investigations on scarf joint behaviour before and after reinforcement are needed aiming to reliable design procedures. In this study, the role of the fastener inside this tension resisting carpentry joint and its contribution in yield strength and stiffness have been investigated. Specific attention has been addressed to stiffness, which is positively influenced by the insertion of timber pegs. Three samples of fir scarf-joints have been tested, each one made of three specimens, with different configurations: without fasteners, with timber pegs and with steel pins. The different failure modes under tension load of the samples and their rheological behaviour have been studied and compared to trace force distribution between the resisting elements, that is the ash key and the added fasteners