COL4A3 Founder Mutations in Greek-Cypriot Families with Thin Basement Membrane Nephropathy and Focal Segmental Glomerulosclerosis Dating from Around 18th Century

2008 ◽  
Vol 12 (2) ◽  
pp. 273-278 ◽  
Author(s):  
Konstantinos Voskarides ◽  
Charalampos Patsias ◽  
Alkis Pierides ◽  
Constantinos Deltas
Keyword(s):  
Basement Membrane ◽  
Focal Segmental Glomerulosclerosis ◽  
18Th Century ◽  
Founder Mutations ◽  
Thin Basement Membrane Nephropathy ◽  
Segmental Glomerulosclerosis ◽  
Greek Cypriot

scholarly journals Clinicopathological Implications of Proteinuria after Long-Term Isolated Hematuria due to Thin Basement Membrane Nephropathy and Focal Segmental Glomerulosclerosis

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Ryo Togashi ◽  
Yoshikazu Nemoto ◽  
Kaito Waki ◽  
Michito Nagura ◽  
Shigeyuki Arai ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Focal Segmental Glomerulosclerosis ◽  
Angiotensin Receptor Blocker ◽  
Kidney Biopsy ◽  
Angiotensin Receptor ◽  
Thin Basement Membrane Nephropathy ◽  
Segmental Glomerulosclerosis ◽  
Features Reduction ◽  
Urinary Abnormalities

A 45-year-old obese man presented with persistent hematuria for 21 years. At the age of 37, he developed hypertension and proteinuria which later increased up to 1.6 g/g creatinine. Kidney biopsy revealed thin basement membrane nephropathy (TBMN) and focal segmental glomerulosclerosis (FSGS), which explained his urinary abnormalities. Although a subgroup of TBMN can be complicated by FSGS, his FSGS was associated with obesity because of its histological features. Reduction of body weight and increasing a dose of angiotensin-receptor blocker could transiently reduce the amount of proteinuria. Clinicopathological implications of proteinuria after long-term hematuria by TBMN and FSGS were further discussed.

scholarly journals COL4A3/COL4A4 Mutations Producing Focal Segmental Glomerulosclerosis and Renal Failure in Thin Basement Membrane Nephropathy

2007 ◽  
Vol 18 (11) ◽  
pp. 3004-3016 ◽  
Author(s):  
Konstantinos Voskarides ◽  
Loukas Damianou ◽  
Vassos Neocleous ◽  
Ioanna Zouvani ◽  
Stalo Christodoulidou ◽  
...  
Keyword(s):  
Renal Failure ◽  
Basement Membrane ◽  
Focal Segmental Glomerulosclerosis ◽  
Thin Basement Membrane Nephropathy ◽  
Segmental Glomerulosclerosis

scholarly journals The use of electron microscopy in the diagnosis of focal segmental glomerulosclerosis: are current pathological techniques missing important abnormalities in the glomerular basement membrane?

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1204
Author(s):  
Justin Davis ◽  
Alwie Tjipto ◽  
Katharine Hegerty ◽  
Andrew Mallett
Keyword(s):  
Electron Microscopy ◽  
Basement Membrane ◽  
Focal Segmental Glomerulosclerosis ◽  
Glomerular Basement Membrane ◽  
Type Iv Collagen ◽  
Histological Diagnosis ◽  
Ultrastructural Changes ◽  
Type Iv ◽  
Segmental Glomerulosclerosis ◽  
Two Samples

Background: There is an increasing appreciation that variants of the COL4A genes may be associated with the development of focal segmental glomerulosclerosis (FSGS). On electron microscopy, such variants may produce characteristic changes within the glomerular basement membrane (GBM). These changes may be missed if glomerular lesions histologically diagnosed as FSGS on light microscopy are not subjected to electron microscopy. Methods: We conducted a retrospective cohort analysis of all patients presenting to two hospitals who received a primary histological diagnosis of FSGS to see if these samples underwent subsequent electron microscopy. Each such sample was also scrutinised for the presence of characteristic changes of an underlying type IV collagen disorder Results: A total of 43 patients were identified. Of these, only 30 underwent electron microscopy. In two samples there were histological changes detected that might have suggested the underlying presence of a type IV collagen disorder. Around one in three biopsy samples that had a histological diagnosis of FSGS were not subjected to electron microscopy. Conclusion: Renal biopsy samples that have a histological diagnosis of primary FSGS not subjected to subsequent electron microscopy may potentially miss ultrastructural changes in the GBM that could signify an underlying type IV collagen disorder as the patient’s underlying disease process. This could potentially affect both them and their families’ investigative and management decisions given potential for implications for transplant, heritability and different disease pathogenesis. This represents a gap in care which should be reflected upon and rectified via iterative standard care and unit-level quality assurance initiatives.

scholarly journals NPHS2 gene polymorphism aggravates renal damage caused by focal segmental glomerulosclerosis with COL4A3 mutation

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Liping Sun ◽  
Xinzhou Zhang ◽  
Zhen Wang
Keyword(s):  
Renal Failure ◽  
Basement Membrane ◽  
Gene Polymorphism ◽  
Focal Segmental Glomerulosclerosis ◽  
Glomerular Basement Membrane ◽  
Renal Damage ◽  
Single Gene ◽  
Filtration Barrier ◽  
Segmental Glomerulosclerosis ◽  
Nphs2 Gene

Abstract Focal segmental glomerulosclerosis (FSGS), a type of primary glomerular disease, is the leading cause of end-stage renal disease (ESRD). Several studies have revealed that certain single-gene mutations are involved in the pathogenesis of FSGS; however, the main cause of FSGS has not been fully elucidated. Homozygous mutations in the glomerular basement membrane gene can lead to early renal failure, while heterozygous carriers develop renal failure symptoms late. Here, molecular genetic analysis of clinical information collected from clinical reports and medical records was performed. Results revealed that nephrosis 2 (NPHS2) gene polymorphism aggravated renal damage in three FSGS families with heterozygous COL4A3 mutation, leading to early renal failure in index patients. Our findings suggest that COL4A3 and NPHS2 may have a synergistic effect on renal injury caused by FSGS. Further analysis of the glomerular filtration barrier could help assess the cause of kidney damage. Moreover, a detailed analysis of the glomerular basement membrane-related genes and podocyte structural proteins may help us better understand FSGS pathogenesis and provide insights into the prognosis and treatment of hereditary glomerulonephropathy.

scholarly journals Kidney Injury by Variants in the COL4A5 Gene Aggravated by Polymorphisms in Slit Diaphragm Genes Causes Focal Segmental Glomerulosclerosis

2019 ◽  
Vol 20 (3) ◽  
pp. 519 ◽  
Author(s):  
Jenny Frese ◽  
Matthias Kettwig ◽  
Hildegard Zappel ◽  
Johannes Hofer ◽  
Hermann-Josef Gröne ◽  
...  
Keyword(s):  
Renal Failure ◽  
Basement Membrane ◽  
Focal Segmental Glomerulosclerosis ◽  
Glomerular Basement Membrane ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Slit Diaphragm ◽  
Filtration Barrier ◽  
Segmental Glomerulosclerosis ◽  
Case Series Study

Kidney injury due to focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular disorder causing end-stage renal disease. Homozygous mutations in either glomerular basement membrane or slit diaphragm genes cause early renal failure. Heterozygous carriers develop renal symptoms late, if at all. In contrast to mutations in slit diaphragm genes, hetero- or hemizygous mutations in the X-chromosomal COL4A5 Alport gene have not yet been recognized as a major cause of kidney injury by FSGS. We identified cases of FSGS that were unexpectedly diagnosed: In addition to mutations in the X-chromosomal COL4A5 type IV collagen gene, nephrin and podocin polymorphisms aggravated kidney damage, leading to FSGS with ruptures of the basement membrane in a toddler and early renal failure in heterozygous girls. The results of our case series study suggest a synergistic role for genes encoding basement membrane and slit diaphragm proteins as a cause of kidney injury due to FSGS. Our results demonstrate that the molecular genetics of different players in the glomerular filtration barrier can be used to evaluate causes of kidney injury. Given the high frequency of X-chromosomal carriers of Alport genes, the analysis of genes involved in the organization of podocyte architecture, the glomerular basement membrane, and the slit diaphragm will further improve our understanding of the pathogenesis of FSGS and guide prognosis of and therapy for hereditary glomerular kidney diseases.

scholarly journals An audit of electron microscopy in the diagnosis of focal segmental glomerulosclerosis: are current pathological techniques missing important abnormalities in the glomerular basement membrane?

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1204
Author(s):  
Justin Davis ◽  
Alwie Tjipto ◽  
Katharine Hegerty ◽  
Andrew Mallett
Keyword(s):  
Electron Microscopy ◽  
Basement Membrane ◽  
Focal Segmental Glomerulosclerosis ◽  
Glomerular Basement Membrane ◽  
Cohort Analysis ◽  
Collagen Iv ◽  
Histological Diagnosis ◽  
Ultrastructural Changes ◽  
Segmental Glomerulosclerosis ◽  
Two Samples

Background: There is an increasing appreciation that variants of the collagen IV genes may be associated with the development of focal segmental glomerulosclerosis (FSGS). On electron microscopy, such variants may produce characteristic changes within the glomerular basement membrane (GBM). These changes may be missed if glomerular lesions histologically diagnosed as FSGS on light microscopy are not subjected to electron microscopy. Methods: We conducted a retrospective cohort analysis of all patients presenting to two hospitals who received a primary histological diagnosis of FSGS to see if these samples underwent subsequent electron microscopy. Each such sample was also scrutinised for the presence of characteristic changes of an underlying collagen IV disorder Results: A total of 43 patients were identified. Of these, only 30 underwent electron microscopy. In two samples there were histological changes detected that might have suggested the underlying presence of a collagen IV disorder. Around one in three biopsy samples that had a histological diagnosis of FSGS were not subjected to electron microscopy. Conclusion: Renal biopsy samples that have a histological diagnosis of primary FSGS not subjected to subsequent electron microscopy may potentially miss ultrastructural changes in the GBM that could signify an underlying collagen IV disorder as the patient’s underlying disease process. This could potentially affect both them and their families’ investigative and management decisions given potential for implications for transplant, heritability and different disease pathogenesis. This represents a gap in care which should be reflected upon and rectified via iterative standard care and unit-level quality assurance initiatives.

Sign in / Sign up

Export Citation Format

Share Document