A novel single amino acid deletion impairs fibronectin function and causes familial glomerulopathy with fibronectin deposits: case report of a family

Abstract Background Glomerulopathy with fibronectin deposits is an autosomal dominant disease associated with proteinuria, hematuria, hypertension and renal function decline. Forty percent of the cases are caused by mutations in FN1, the gene that encodes fibronectin. Case presentation This report describes two cases of Glomerulopathy with fibronectin deposits, involving a 47-year-old father and a 14-year-old son. The renal biopsies showed glomeruli with endocapillary hypercellularity and large amounts of mesangial and subendothelial eosinophilic deposits. Immunohistochemistry for fibronectin was markedly positive. Whole exome sequencing identified a novel FN1 mutation that leads to an amino-acid deletion in both patients (Ile1988del), a variant that required primary amino-acid sequence analysis for assessment of pathogenicity. Our primary sequence analyses revealed that Ile1988 is very highly conserved among relative sequences and is positioned in a C-terminal FN3 domain containing heparin- and fibulin-1-binding sites. This mutation was predicted as deleterious and molecular mechanics simulations support that it can change the tertiary structure and affect the complex folding and its molecular functionality. Conclusion The current report not only documents the occurrence of two GFND cases in an affected family and deeply characterizes its anatomopathological features but also identifies a novel pathogenic mutation in FN1, analyzes its structural and functional implications, and supports its pathogenicity.https://deepblue.lib.umich.edu/bitstream/2027.42/152212/1/12882_2019_Article_1507.pd

Social, Human and Positive Psychological Capital in the Labour Market Re-integration of People Deported to the Dominican Republic

More than six million people have been deported from the United States since 1996. The Dominican Republic is one of the top ten countries to which deportees are sent. Most scholarship on deportation focuses on the challenges deportees face post-deportation. There is also a long history of scholarship on how migrants draw from social, human and financial capital to integrate into host societies. This article thus asks what forms of capital are useful for deportees’ re-integration and focuses on the forms of capital deportees draw from to survive in the aftermath of deportation. An analysis of 60 in-depth interviews with Dominican deportees reveals how deportees’ combination of limited human capital, fractured social capital and positive psychological capital assists in their re-integration. Results also show that access to employment is not only an important step in social and economic integration, but that it also helps deportees to achieve emotional stability