Finding Down Syndrome Cell Adhesion Molecule (DSCAM) Protein Interactions in Pathways of Neuronal Development

Down Syndrome cell adhesion molecule (DSCAM) is a transmembrane protein that has a significant role in proper neurodevelopment by promoting self-avoidance in neurons. This project aims to identify proteins that interact with DSCAM in the mouse brain by using a library of plasmids. The plasmid library was tested for proteins that interact with the C-terminus end of DSCAM in Brewer’s yeast (S. cerevisiae). By using the bait and prey method from a yeast two-hybrid system, mouse brain proteins were tested for true interaction with DSCAM. Proteins that interact with DSCAM allow the yeast to produce their own leucine, which aids in the growth of the yeast on selective media. Proteins that have been identified as possible protein interactors include COX5B, NEFL, ELAV1, and SOD1, among others. By identifying interactions between unknown proteins and DSCAM, we will be better able to map out the protein interactions that lead to the proper development of the brain

Outcomes of Nephrolithiasis Care by Patient Race: From a Statewide Quality Improvement Collaborative

Kidney stone disease, or nephrolithiasis, is a condition that commonly affects people in the United States. Kentucky is part of the “Kidney Stone Belt”, which has the highest prevalence of kidney stones in the United States. As a member of this region, the state of Kentucky must analyze the quality of nephrolithiasis care provided in the state. Although kidney stone formation is a multifactorial process, efforts must be made to provide consistent care that is in accordance with American Urological Association (AUA) guidelines. Our study is a collaborative effort between Kentucky’s two largest academic medical institutions and aims to reveal the inadequacies of our approach to care today. We completed a retrospective chart review of 429 nephrolithiasis patients of 13 urologists affiliated with two academic medical institutions. Data included aspects of care conducted during the continuum of nephrolithiasis care, and the data was stored in a database. The data was analyzed and stratified by race using the chi-squared test. The racial breakdown of our patient population, which consisted of 429 patients, included the following: 359 Caucasian, 55 African American (AA), and 15 Other. We noted statistically significant differences between races in the following areas of nephrolithiasis care: kidney stone analysis, orders for 24-hour urine tests, and dietary histories. Although not statistically significant, our entire patient population had little to no documentation of physician-led counseling for nephrolithiasis prevention. Our analysis points to various areas in which patients could benefit from quality improvement measures and adherence to AUA guideline practices

Correction to: An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids (Genetics in Medicine, (2021), 23, 4, (740-750), 10.1038/s41436-020-01027-3)

In the original author list, Seth Perlman’s degrees were listed as MD, PhD. Dr Perlman’s degree is MD. The original version has been corrected

An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids

Purpose: In this study we investigate the disease etiology in 12 patients with de novo variants in FAR1 all resulting in an amino acid change at position 480 (p.Arg480Cys/His/Leu). Methods: Following next-generation sequencing and clinical phenotyping, functional characterization was performed in patients’ fibroblasts using FAR1 enzyme analysis, FAR1 immunoblotting/immunofluorescence, and lipidomics. Results: All patients had spastic paraparesis and bilateral congenital/juvenile cataracts, in most combined with speech and gross motor developmental delay and truncal hypotonia. FAR1 deficiency caused by biallelic variants results in defective ether lipid synthesis and plasmalogen deficiency. In contrast, patients’ fibroblasts with the de novo FAR1 variants showed elevated plasmalogen levels. Further functional studies in fibroblasts showed that these variants cause a disruption of the plasmalogen-dependent feedback regulation of FAR1 protein levels leading to uncontrolled ether lipid production. Conclusion: Heterozygous de novo variants affecting the Arg480 residue of FAR1 lead to an autosomal dominant disorder with a different disease mechanism than that of recessive FAR1 deficiency and a diametrically opposed biochemical phenotype. Our findings show that for patients with spastic paraparesis and bilateral cataracts, FAR1 should be considered as a candidate gene and added to gene panels for hereditary spastic paraplegia, cerebral palsy, and juvenile cataracts