This report describes focal segmental glomerulosclerosis 4, susceptibility to (FSGS4), which is a subtype of focal segmental glomerulosclerosis. The human gene implicated in this disease is apolipoprotein L-1 (APOL1), a secreted high-density lipoprotein that may play a role in lipid exchange and transport throughout the body. No gene orthologous to APOL1 has been identified in Drosophila.
Multiple UAS constructs of human Hsap\APOL1 have been introduced into flies, including wild-type (G0) the two variants (G1 and G2) associated with FSGS4, and a C-terminal truncation. Overexpression has been induced using a variety of tissue-specific GAL4 drivers, including 2 different ubiquitous drivers. Phenotypes follow a spectrum, with the truncation variant being the most benign, the wild-type gene producing some deleterious phenotypes, and the FSGS4-associated variants producing more extreme deleterious phenotypes. Overexpression in nephrocytes initially produces as increase in uptake efficiency (based on an ANF-RFP filtration assay), however as the animals age, nephrocyte function declines, nephrocyte cell size increases (hypertrophy), and nephrocytes die prematurely.
Variant(s) implicated in human disease tested (as transgenic human gene, APOL1): the S342G+I384M (G1) and del.N388/Y389 (G2) variant forms have been introduced into flies. G1 carries two missense mutations within the SRA-binding domain; G2 carries a 2-amino-acid deletion within the SRA-binding domain.
[updated Jul. 2018 by FlyBase; FBrf0222196]
Focal segmental glomerulosclerosis is one of many diseases and conditions can affect kidney function by attacking and damaging the glomeruli. "Glomerulosclerosis" refers to a hardening and scarring of the glomeruli. The scarring of FSGS takes place in small sections of each glomerulus, and only a limited number of glomeruli are damaged initially (https://www.kidney.org/atoz/content/focal).
A definitive diagnosis of FSGS is established only by histopathology findings (http://emedicine.medscape.com/article/245915-overview).
Focal segmental glomerulosclerosis (FSGS) is a pathologic finding in several renal disorders that manifest clinically as proteinuria and progressive decline in renal function. Some patients with FSGS develop nephrotic syndrome, which includes massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema. However, patients with FSGS may have proteinuria in the nephrotic range without other features of the nephrotic syndrome (summary by D'Agati et al., 2004, pubmed:14750104; Mathis et al., 1998, pubmed:9461087). [from MIM:603278; 2017.09.14]
Focal segmental glomerulosclerosis is a common cause of end-stage renal disease (Meyrier, 2005; pubmed:16932363). [from MIM:607832; 2017.09.14]
In the literature, the clinical term 'nephrotic syndrome' (NPHS) and the pathologic term 'focal segmental glomerulosclerosis' (FSGS) have often been used to refer to the same disease entity. In OMIM, these disorders are classified as NPHS or FSGS according to how they were first designated in the literature. [from MIM:607832; 2017.09.14]
[FOCAL SEGMENTAL GLOMERULOSCLEROSIS 4, SUSCEPTIBILITY TO; FSGS4](https://omim.org/entry/612551)
[APOLIPOPROTEIN L1; APOL1](https://omim.org/entry/603743)
Susceptibility to this form of FSGS is prevalent in populations of African ancestry, since the same APOL1 variants confer protection against infection with T. b. rhodesiense, a human-specific Trypanosoma subspecies. [from MIM:612551; 2018.07.10]
Susceptibility to this form of renal disease, referred to here as focal segmental glomerulosclerosis-4 (FSGS4), is conferred by specific variants in the APOL1 gene. The variants are designated G1 and G2; both result in changes in the last exon of APOL1. [from MIM:612551 and MIM:603743; 2018.07.10]
APOL1 (Apolipoprotein L-1) encodes a secreted high-density lipoprotein which binds to apolipoprotein A-I. Apolipoprotein A-I is a relatively abundant plasma protein and is the major apoprotein of HDL. APOL1 may play a role in lipid exchange and transport throughout the body. [Gene Cards, APOL1; 2018.07.10]
No gene orthologous to human APOL1 has been identified in Drosophila.
