Diagnostic utility and reporting recommendations for clinical DNA methylation episignature testing in genetically undiagnosed rare diseases.

Purpose: This study aims to assess the diagnostic utility and provide reporting recommendations for clinical DNA methylation episignature testing based on the cohort of patients tested through the EpiSign Clinical Testing Network.

Methods: The EpiSign assay utilized unsupervised clustering techniques and a support vector machine-based classification algorithm to compare each patient's genome-wide DNA methylation profile with the EpiSign Knowledge Database, yielding the result that was reported. An international working group, representing distinct EpiSign Clinical Testing Network health jurisdictions, collaborated to establish recommendations for interpretation and reporting of episignature testing.

Synthetic Control of the Defect Structure and Hierarchical Extra-Large-/Small-Pore Microporosity in Aluminosilicate Zeolite SWY.

The SWY-type aluminosilicate zeolite, STA-30, has been synthesized via different routes to understand its defect chemistry and solid acidity. The synthetic parameters varied were the gel aging, the Al source, and the organic structure directing agent. All syntheses give crystalline materials with similar Si/Al ratios (6-7) that are stable in the activated K,H-form and closely similar by powder X-ray diffraction.

DNA methylation episignature for Witteveen-Kolk syndrome due to SIN3A haploinsufficiency.

Purpose: Witteveen-Kolk syndrome (WITKOS) is a rare, autosomal dominant neurodevelopmental disorder caused by heterozygous loss-of-function alterations in the SIN3A gene. WITKOS has variable expressivity that commonly overlaps with other neurodevelopmental disorders. In this study, we characterized a distinct DNA methylation epigenetic signature (episignature) distinguishing WITKOS from unaffected individuals as well as individuals with other neurodevelopmental disorders with episignatures and described 9 previously unpublished individuals with SIN3A haploinsufficiency.

Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders.

Overlapping clinical phenotypes and an expanding breadth and complexity of genomic associations are a growing challenge in the diagnosis and clinical management of Mendelian disorders. The functional consequences and clinical impacts of genomic variation may involve unique, disorder-specific, genomic DNA methylation episignatures. In this study, we describe 19 novel episignature disorders and compare the findings alongside 38 previously established episignatures for a total of 57 episignatures associated with 65 genetic syndromes.

Near complete deletion of KMT2D in a college student.

Pathogenic variants in KMT2D are typically associated with Kabuki syndrome (KS), a rare multisystem disorder. KS is characterized by facial dysmorphisms, intellectual disability, skeletal and dermatoglyphic differences, and poor growth. Seventy percent of individuals with clinically diagnosed KS have a confirmed pathogenic variant in KMT2D or less commonly KDM6A.

Clinical epigenomics: genome-wide DNA methylation analysis for the diagnosis of Mendelian disorders.

Purpose: We describe the clinical implementation of genome-wide DNA methylation analysis in rare disorders across the EpiSign diagnostic laboratory network and the assessment of results and clinical impact in the first subjects tested.

Methods: We outline the logistics and data flow between an integrated network of clinical diagnostics laboratories in Europe, the United States, and Canada. We describe the clinical validation of EpiSign using 211 specimens and assess the test performance and diagnostic yield in the first 207 subjects tested involving two patient subgroups: the targeted cohort (subjects with previous ambiguous/inconclusive genetic findings including genetic variants of unknown clinical significance) and the screening cohort (subjects with clinical findings consistent with hereditary neurodevelopmental syndromes and no previous conclusive genetic findings).

Techniques for direct experimental evaluation of structure-transport relationships in disordered porous solids.

Determining structure-transport relationships is critical to optimising the activity and selectivity performance of porous pellets acting as heterogeneous catalysts for diffusion-limited reactions. For amorphous porous systems determining the impact of particular aspects of the void space on mass transport often requires complex characterization and modelling steps to deconvolve the specific influence of the feature in question. These characterization and modelling steps often have limited accuracy and precision.

Improving sensitivity and accuracy of pore structural characterisation using scanning curves in integrated gas sorption and mercury porosimetry experiments.

Gas sorption scanning curves are increasingly used as a means to supplement the pore structural information implicit in boundary adsorption and desorption isotherms to obtain more detailed pore space descriptors for disordered solids. However, co-operative adsorption phenomena set fundamental limits to the level of information that conventional scanning curve experiments can deliver. In this work, we use the novel integrated gas sorption and mercury porosimetry technique to show that crossing scanning curves are obtained for some through ink-bottle pores within a disordered solid, thence demonstrating that their shielded pore bodies are undetectable using conventional scanning experiments.

Simulation of nonwetting phase entrapment within porous media using magnetic resonance imaging.

Models representing the pore structures of amorphous, mesoporous silica pellets have been constructed using magnetic resonance images of the materials. Using magnetic resonance imaging (MRI), maps of the macroscopic (approximately 0.01-1 mm) spatial distribution of porosity and pore size were obtained.

Characterization of Macroscopic Structural Disorder in Porous Media Using Mercury Porosimetry.

A new structural model for the interpretation of mercury porosimetry data for samples having a bimodal pore size distribution is presented. The morphology of the macropore network of a porous solid has been studied using a combination of mercury porosimetry and NMR techniques. The model consists of a lattice-based network of pore bodies and pore necks.