Mexican patient with Ellis-van Creveld syndrome and cleft palate: Importance of functional hemizygosity and phenotype expansion.

BACKGROUND: Ellis-van Creveld syndrome (EvCS) is a chondroectodermal dysplasia caused by germline pathogenic variants in ciliary complex subunit 1 and 2 genes (EVC, EVC2) on chromosome 4p16.2. This disease has a broad phenotype, and there are few described phenotype-genotype correlations. METHODS: Ethical Compliance: Written informed consent was obtained from the parents. Here, we report a genetically confirmed Mexican patient with EvCS having two inherited pathogenic variants in trans in EVC2: c.[1195C>T];[2161delC]. RESULTS: This patient allowed a genotypic-phenotypic comparison with another Mexican subject who presented a more attenuated phenotype; furthermore, our patient also presented cleft palate, a rarely reported feature. CONCLUSION: Our case shows the importance of comparing functional hemizygosity between patient's phenotypes when they share a variant, and our case also supports the association of alterations in the palate as part of the EvCS phenotype.

Anionic nanoparticle and microplastic non-exponential distributions from source scale with grain size in environmental granular media.

Nanoparticle and microplastic (colloid) transport behaviors impact strategies for groundwater protection and remediation. Complex colloid transport behaviors of anionic nano- and micro-sized colloids have been previously elucidated via independent experiments in chemically-cleaned and amended granular media with grain sizes in the range of fine to coarse sand (e.g., 200-1000 µm). Such experiments show that under conditions where a repulsive barrier was present in colloid-collector interactions (unfavorable conditions), the distribution of retained colloids down-gradient from their source deviates from the exponential decrease expected from compounded loss across a series of collectors (grains). Previous experiments have not examined the impact of colloid size or granular media grain size on colloid distribution down-gradient from their source, particularly in streambed-equilibrated granular media. To address this gap, a field transport experiment in constructed wetland stream beds to distances up to 20 m were conducted for colloids ranging in size from micro to nano (60 nm-7 µm) in streambed-equilibrated pea gravel and sand (4200 and 420 µm mean grain sizes, respectively). All colloid sizes showed non-exponential (hyper-exponential) distributions from source, over meter scales in pea gravel versus cm scales reported for fine sand. Colloids in the ca. 1 µm size range were most mobile, as expected from mass transfer to surfaces and interaction with nanoscale heterogeneity. The distance over which non-exponential colloid distribution occurred increased with media grain size, which carries implications for the potential mechanism driving non-exponential colloid distribution from source, and for strategies to predict transport.

A Unified Force and Torque Balance for Colloid Transport: Predicting Attachment and Mobilization under Favorable and Unfavorable Conditions.

Colloid attachment and detachment behaviors concern a wide range of environmental contexts but have typically been mechanistically predicted exclusive of one another despite their obvious coupling. Furthermore, previous mechanistic prediction often addressed packed column contexts, wherein specific forces and torques on the colloid could not be well-constrained, preventing robust predictions. These weaknesses were addressed through direct observation experiments under conditions where perfect sink assumptions fail and allow calibration of the contact between the colloid and collector. Attachment and flow perturbation experiments in the presence of colloid-collector attraction (favorable conditions) permitted calibration of contact parameters without the complexity that comes with colloid-collector repulsion (unfavorable conditions). Combining calibrated contact parameters with discrete representative nanoscale heterogeneity, developed to predict unfavorable attachment, provided an independent means to predict unfavorable detachment. The result was mechanistic prediction of colloid attachment and detachment that quantitatively agreed with experimental observation for both ionic strength and flow perturbation results, improving significantly upon previous qualitative prediction.

Hydrodynamic versus Surface Interaction Impacts of Roughness in Closing the Gap between Favorable and Unfavorable Colloid Transport Conditions.

Recent experiments revealed that roughness decreases the gap in colloid attachment between favorable (repulsion absent) and unfavorable (repulsion present) conditions through a combination of hydrodynamic slip and surface interactions with asperities. Hydrodynamic slip was calibrated to experimentally observed tangential colloid velocities, demonstrating that slip length was equal to maximum asperity relief, thereby providing a functional relationship between slip and roughness metrics. Incorporation of the slip length in mechanistic particle trajectory simulations yielded the observed modest decrease in attachment over rough surfaces under favorable conditions, with the observed decreased attachment being due to reduced colloid delivery rather than decreased attraction. Cumulative interactions with multiple asperities acting within the zone of colloid-surface interaction were unable to produce the observed dramatic increased attachment and decreased reversibility with increased roughness under unfavorable conditions, necessitating inclusion of nanoscale attractive heterogeneity that was inferred to have codeveloped with roughness. Simulated attachment matched experimental observations when the spatial frequency of larger heterodomains (nanoscale zones of attraction) increased disproportionately relative to smaller heterodomains as roughness increased, whereas attachment was insensitive to asperity properties, including the number of interactions per asperity and asperity height; colloid detachment simulations were highly sensitive to these parameters. These cumulative findings reveal that hydrodynamic slip moderately decreases colloid bulk delivery, nanoscale heterogeneity dramatically enhances colloid attachment, and multiple interactions among asperities decrease detachment from rough surfaces.