Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Purpose Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Purpose: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome

A Distinctive Binary Descriptor and Two-Point RANSACWC for Point Cloud Registration

Point cloud registration is a fundamental problem in many applications. The point cloud registration based on local shape descriptor has been widely researched. In order to further improve the performance of registration, a novel registration method is proposed in this article. First, a binary descriptor is designed to establish correspondences between two point clouds. The descriptor has high descriptiveness. Thus, more correct correspondences are established. Then, a 3-D transformation estimation technique is developed, in which multiple constraints are used to accelerate the computation. When the randomly selected correspondences do not satisfy the constraints, the iteration is skipped. Finally, the experiments are performed to analyze the descriptor and 3-D transformation estimation technique. The comparison with the existing descriptors is implemented on three datasets. The results demonstrate that our descriptor has better matching performance. As for the 3-D transformation estimation technique, the combinations of the constraints are first analyzed. The performance of different constraints is presented and the best combination is chose. The comparative results with the existing techniques demonstrate that the proposed 3-D transformation estimation technique can obtain better registration accuracy and computation efficiency

Tuning Electronic Structures of BN and C Double-Wall Hetero-Nanotubes

First principle calculations based on density functional theory with the generalized gradient approximation were carried out to investigate the energetic and electronic properties of carbon and boron nitride double-wall hetero-nanotubes (C/BN-DWHNTs) with different chirality and size, including an armchair (n, n) carbon nanotube (CNT) enclosed in (m, m) boron nitride nanotube (BNNT) and a zigzag (n, 0) CNT enclosed in (m, 0) BNNT. The electronic structure of these DWHNTs under a transverse electric field was also investigated. The ability to tune the band gap with changing the intertube distance (di) and imposing an external electric field (F) of zigzag DWHNTs provides the possibility for future electronic and electrooptic nanodevice applications

Table_1_Rapid visual detection of Enterocytozoon hepatopenaei by recombinase polymerase amplification combined with lateral flow dipstick.docx

Enterocytozoon hepatopenaei (EHP) is a high-impact pathogen in shrimp farming, causing huge economic losses to the global shrimp farming industry every year. However, current EHP detection methods are primarily based on the development of polymerase chain reaction (PCR) techniques that rely on sophisticated and expensive instruments. Consequently, a rapid, practical, and sensitive protocol for the detection of EHP is necessary. Recombinase polymerase amplification combined with a lateral flow dipstick (LFD-RPA) assay was developed using a pair of primers and nfo-probe targeting the conserved region of the spore wall protein gene. Under optimized reaction conditions, the LFD-RPA assay can detect 10 copies/μL of standard plasmid within 20 min at 40°C. Furthermore, the specificity of the LFD-RPA was also verified with other common pathogens of shrimp. Thirty-nine samples of Litopenaeus vannamei were collected in shrimp farms and detected using LFD-RPA and nested PCR. Thirty-two positive samples were detected by LFD-RPA. Compared with those of nested PCR, the diagnostic sensitivity and specificity of LFD-RPA were 100% and 100%, respectively. These results indicated the great application potential of the newly developed LFD-RPA assay for point-of-care diagnosis, epidemic surveillance, and epidemiological investigation of EHP.</p

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Purpose: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome