Variant characterisation and clinical profile in a large cohort of patients with Ellis-van Creveld syndrome and a family with Weyers acrofacial dysostosis.

BACKGROUND: Ellis-van Creveld syndrome (EvC) is a recessive disorder characterised by acromesomelic limb shortening, postaxial polydactyly, nail-teeth dysplasia and congenital cardiac defects, primarily caused by pathogenic variants in EVC or EVC2. Weyers acrofacial dysostosis (WAD) is an ultra-rare dominant condition allelic to EvC. The present work aimed to enhance current knowledge on the clinical manifestations of EvC and WAD and broaden their mutational spectrum. METHODS: We conducted molecular studies in 46 individuals from 43 unrelated families with a preliminary clinical diagnosis of EvC and 3 affected individuals from a family with WAD and retrospectively analysed clinical data. The deleterious effect of selected variants of uncertain significance was evaluated by cellular assays. MAIN RESULTS: We identified pathogenic variants in EVC/EVC2 in affected individuals from 41 of the 43 families with EvC. Patients from each of the two remaining families were found with a homozygous splicing variant in WDR35 and a de novo heterozygous frameshift variant in GLI3, respectively. The phenotype of these patients showed a remarkable overlap with EvC. A novel EVC2 C-terminal truncating variant was identified in the family with WAD. Deep phenotyping of the cohort recapitulated 'classical EvC findings' in the literature and highlighted findings previously undescribed or rarely described as part of EvC. CONCLUSIONS: This study presents the largest cohort of living patients with EvC to date, contributing to better understanding of the full clinical spectrum of EvC. We also provide comprehensive information on the EVC/EVC2 mutational landscape and add GLI3 to the list of genes associated with EvC-like phenotypes.

Engineering of the Central Core on DBD-Based Materials with Improved Power-Conversion Efficiency by Using the DFT Approach.

Developing proficient organic solar cells with improved optoelectronic properties is still a matter of concern. In the current study, with an aspiration to boost the optoelectronic properties and proficiency of organic solar cells, seven new small-molecule acceptors (Db1-Db7) are presented by altering the central core of the reference molecule (DBD-4F). The optoelectronic aspects of DBD-4F and Db1-Db7 molecules were explored using the density functional theory (DFT) approach, and solvent-state calculations were assessed utilizing TD-SCF simulations. It was noted that improvement in photovoltaic features was achieved by designing these molecules. The results revealed a bathochromic shift in absorption maxima (λmax) of designed molecules reaching up to 776 nm compared to 736 nm of DBD-4F. Similarly, a narrow band gap, low excitation energy, and reduced binding energy were also observed in newly developed molecules in comparison with the pre-existing DBD-4F molecule. Performance improvement can be indicated by the high light-harvesting efficiency (LHE) of designed molecules (ranging from 0.9992 to 0.9996 eV) compared to the reference having a 0.9991 eV LHE. Db4 and Db5 exhibited surprisingly improved open-circuit voltage (V OC) values up to 1.64 and 1.67 eV and a fill factor of 0.9198 and 0.9210, respectively. Consequently, these newly designed molecules can be considered in the future for practical use in manufacturing OSCs with improved optoelectronic and photovoltaic attributes.