ROBO2 Gene Variants Are Associated with Familial Vesicoureteral Reflux

The SLIT2 receptor ROBO2 plays a key role in the formation of the ureteric bud, and its inactivation in mice leads to supernumerary ureteric bud development, lack of ureter remodeling, and improper insertion of the ureters into the bladder. Recently, two heterozygous ROBO2 missense mutations were identified in two families with primary vesicoureteral reflux occurring in combination with congenital anomalies of the kidney and urinary tract (VUR/CAKUT). This study investigated a possible causal role of ROBO2 gene variants in 95 unrelated patients with primary VUR (n = 78) or VUR/CAKUT. Eighty-two percent of all patients had a family history of genitourinary anomalies. Twenty-four ROBO2 gene variants were identified by direct sequencing of all 26 exons and the exon-intron boundaries. Of these, four led to amino acid substitutions: Gly328Ser, Asn515Ile, Asp766Gly, and Arg797Gln. When the families were examined, the missense variants co-segregated with VUR (three families) or VUR/CAKUT (one family). These variants were not found in 190 control subjects, and the affected amino acids have been conserved through evolution. In conclusion, a relatively high frequency of ROBO2 variants (5.1%) was found in familial cases; however, functional studies and validation in other cohorts are warranted

Association of migraine-like headaches with Schimke immuno-osseous dysplasia

Schimke immuno-osseous dysplasia (SIOD) is characterized by spondyloepiphyseal. dysplasia, nephropathy, and T-cell deficiency. SIOD is caused by mutations in the putative chromatin remodeling protein SAL&RCAL1. We report an 8-year-old boy with SIOD and recurrent, severe, refractory migraine-like headaches. Through a retrospective questionnaire-based study, we found that refractory and severely disabling migraine-like headaches occur in nearly half of SIOD patients. We have also found that the vasodilator minoxidil provided symptomatic relief for one patient. We hypothesize that these headaches may arise from an intrinsic vascular, neuroimmune, or neurovascular defect resulting from loss of SMARCAL1 function

CULTURAL HERITAGE LEADING URBAN FUTURES Actions and Innovations from ROCK PROJECT

The ROCK project sees historic city centres as laboratories to demonstrate how Cultural Heritage can be an engine of regeneration, sustainable development and economic growth. ROCK approach foresees the systemic and flexible application of a series of role-model practices in the testing sites of three Replicator cities, to turn historic city centres afflicted by physical decay, social conflicts and poor life quality into Creative and Sustainable Districts. This book provides an overview of the project, extracting themes, material and final remarks from the Open Knowledge Week \u201cCultural Heritage Leading Urban Futures\u201d, held on 27-30 October 2020. Over the past three years, ten ROCK cities \u2013 Athens, Bologna, Cluj-Napoca, Eindhoven, Lisbon, Liverpool, Lyon, Skopje, Turin, and Vilnius \u2013 together with service providers and knowledge brokers have tested and advanced numerous soft and hard tools, collaborative approaches aimed at shaping sustainable, heritage-led urban futures. This book shows their shared results, best practices and lessons learnt from interdisciplinary research, innovative action, dissemination of knowledge and creation of new synergies at the European level

Lack of IL7R alpha expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD)

Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive, fatal childhood disorder associated with skeletal dysplasia, renal dysfunction, and T-cell immunodeficiency. This disease is linked to biallelic loss-of-function mutations of the SMARCAL1 gene. Although recurrent infection, due to T-cell deficiency, is a leading cause of morbidity and mortality, the etiology of the T-cell immunodeficiency is unclear. Here, we demonstrate that the T cells of SIOD patients have undetectable levels of protein and mRNA for the IL-7 receptor alpha chain (IL7R alpha) and are unresponsive to stimulation with IL-7, indicating a loss of functional receptor. No pathogenic mutations were detected in the exons of IL7R in these patients; however, CpG sites in the IL7R promoter were hypermethylated in SIOD T cells. We propose therefore that the lack of IL7R alpha expression, associated with hypermethylation of the IL7R promoter, in T cells and possibly their earlier progenitors, restricts T-cell development in SIOD patients. (C) 2015 Elsevier Inc. All rights reserved