A Novel LMX1B Variant Identified in a Patient Presenting with Severe Renal Involvement and Thin Glomerular Basement Membrane

Nephron ◽  
2021 ◽  
pp. 1-7
Author(s):  
Nobuhisa Morimoto ◽  
Kiyotaka Nagahama ◽  
Takayasu Mori ◽  
Takuya Fujimaru ◽  
Yukio Tsuura ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Renal Biopsy ◽  
Glomerular Basement Membrane ◽  
Kidney Diseases ◽  
Renal Involvement ◽  
Renal Tubules ◽  
Persistent Proteinuria ◽  
Previous Diagnosis ◽  
Heterozygous Variant ◽  
Nail Patella Syndrome

We report a case of nail-patella syndrome (NPS) with unusual thinning of the glomerular basement membrane (GBM) associated with a novel heterozygous variant in the <i>LMX1B</i> gene. A 43-year-old female patient with a previous diagnosis of NPS, referred to our hospital for persistent proteinuria, underwent a renal biopsy, which revealed minor glomerular abnormalities. She underwent a second renal biopsy at the age of 56 owing to the presence of persistent proteinuria and decline in serum albumin, meeting the diagnostic criteria for nephrotic syndrome. Light microscopy demonstrated glomerulosclerosis and cystic dilatation of the renal tubules. Notably, electron microscopy revealed unusual thinning of the GBM, which is quite different from typical biopsy findings observed in patients with NPS, characterized by thick GBM with fibrillary material and electron-lucent structures. Comprehensive genetic screening for 168 known genes responsible for inherited kidney diseases using a next-generation sequencing panel identified a novel heterozygous in-frame deletion-insertion (c.723_729delinsCAAC: p.[Ser242_Lys243delinsAsn]) in exon 4 of the <i>LMX1B</i> gene, which may account for the disrupted GBM structure. Further studies are warranted to elucidate the complex genotype-phenotype relationship between <i>LMX1B</i> and proper GBM morphogenesis.

Thin glomerular basement membrane nephropathy and other collagenopathies

2018 ◽  
Author(s):  
Laurence Heidet ◽  
Bertrand Knebelmann ◽  
Marie Claire Gubler
Keyword(s):  
Basement Membrane ◽  
Renal Disease ◽  
Renal Biopsy ◽  
Glomerular Basement Membrane ◽  
Alport Syndrome ◽  
Autosomal Dominant ◽  
Increased Risk ◽  
Autosomal Dominant Fashion ◽  
Nail Patella Syndrome

The discovery of a thin glomerular basement membrane in a renal biopsy without any other abnormalities can be explained in a number of ways. This could be an early biopsy in a patient with Alport syndrome, or it could be an individual who is a carrier for an Alport gene. These carriers are at increased risk of significant renal disease in their lifetime and some have proteinuria as well as haematuria, so they can no longer be equated with the historic label of benign familial haematuria. Some families with a thin glomerular basement membrane and haematuria inherited in an autosomal dominant fashion do not appear to have linkage to COL4 genes. Others have variable renal disease that has sometimes given rise to a label of mild but autosomal dominant Alport syndrome. This territory might also attract the label basement membrane 345 collagenopathy. Other uncommon conditions affecting the glomerular basement membrane include nail patella syndrome.

scholarly journals SP044MICRO-RNA REGULATED INTERACTIONS BETWEEN PODOCYTES AND GLOMERULAR BASEMENT MEMBRANE IN PROTEINURIC KIDNEY DISEASES

2015 ◽  
Vol 30 (suppl_3) ◽  
pp. iii395-iii395
Author(s):  
Janina Müller-Deile ◽  
Jan Dannenberg ◽  
Jenny Nystrom ◽  
Peidi Liu ◽  
Johan Lorenzen ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Kidney Diseases

scholarly journals Albumin contributes to kidney disease progression in Alport syndrome

2016 ◽  
Vol 311 (1) ◽  
pp. F120-F130 ◽  
Author(s):  
George Jarad ◽  
Russell H. Knutsen ◽  
Robert P. Mecham ◽  
Jeffrey H. Miner
Keyword(s):  
Kidney Disease ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Alport Syndrome ◽  
Transforming Growth Factor ◽  
Kidney Diseases ◽  
Serum Triglyceride ◽  
Transforming Growth Factor Β ◽  
Collagen Type Iv ◽  
Albumin Concentration

Alport syndrome is a familial kidney disease caused by defects in the collagen type IV network of the glomerular basement membrane. Lack of collagen-α3α4α5(IV) changes the glomerular basement membrane morphologically and functionally, rendering it leaky to albumin and other plasma proteins. Filtered albumin has been suggested to be a cause of the glomerular and tubular injuries observed at advanced stages of Alport syndrome. To directly investigate the role that albumin plays in the progression of disease in Alport syndrome, we generated albumin knockout ( Alb−/−) mice to use as a tool for removing albuminuria as a component of kidney disease. Mice lacking albumin were healthy and indistinguishable from control littermates, although they developed hypertriglyceridemia. Dyslipidemia was observed in Alb+/− mice, which displayed half the normal plasma albumin concentration. Alb mutant mice were bred to collagen-α3(IV) knockout ( Col4a3−/−) mice, which are a model for human Alport syndrome. Lack of circulating and filtered albumin in Col4a3−/−; Alb−/− mice resulted in dramatically improved kidney disease outcomes, as these mice lived 64% longer than did Col4a3−/−; Alb+/+ and Col4a3−/−; Alb+/− mice, despite similar blood pressures and serum triglyceride levels. Further investigations showed that the absence of albumin correlated with reduced transforming growth factor-β1 signaling as well as reduced tubulointerstitial, glomerular, and podocyte pathology. We conclude that filtered albumin is injurious to kidney cells in Alport syndrome and perhaps in other proteinuric kidney diseases, including diabetic nephropathy.

Regulation of glomerular basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome

10.1038/84853 ◽  
2001 ◽  
Vol 27 (2) ◽  
pp. 205-208 ◽  
Author(s):  
Roy Morello ◽  
Guang Zhou ◽  
Sandra D. Dreyer ◽  
Scott J. Harvey ◽  
Yoshifumi Ninomiya ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Renal Disease ◽  
Glomerular Basement Membrane ◽  
Collagen Expression ◽  
Basement Membrane Collagen ◽  
Nail Patella Syndrome ◽  
Membrane Collagen

Variability of the Antigenicity of the Glomerular Basement Membrane in Nail-patella Syndrome

1989 ◽  
Vol 4 (4) ◽  
pp. 262-265 ◽  
Author(s):  
N. P. Sutcliffe ◽  
S. J. Cashman ◽  
C. O. S. Savage ◽  
J. G. Fox ◽  
J. M. Boulton-Jones
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Nail Patella Syndrome

scholarly journals RETRACTED: Production and Characterization of Recombinant Rat Non-collagen Domain of α3 Chain of Type IV Collagen α3 (IV) NC1 Antigen

2016 ◽  
Vol 12 (24) ◽  
pp. 98
Author(s):  
Afsana Munni
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Type Iv Collagen ◽  
Kidney Diseases ◽  
Cell Epitope ◽  
Affinity Column ◽  
Igg Antibody ◽  
Amino Terminal ◽  
Type Iv ◽  
Collagenous Domain

Glomerulonephritis disease is characterized by inflammation of glomeruli or small blood vessels in the kidney which causes kidney diseases. Glomerulonephritis disease deposits the anti-GBM auto antibody in the glomerular basement membrane. The type IV collagen is the main component of glomerular basement membrane that has α3 chain of type (IV) collagen of non-collagenous domain which contains N-terminal 7S domain, a triple helical collagenous domain, and a C- terminal non-collagenous glomerular domain (NC1). The amino terminal of α3 (IV) NC1 that induces the experimental autoimmuno glomerulonephritis (EAG) in rat model has been identified. The recombinant rat α3 (IV)NC1 antigen has nine amino acid span that is consistent with antibody or T cell epitope which is induced in EAG. The research is carried out on the recombinant rat α3 (IV) NC1 production, purification, quantification, and characterization. The circulation of Anti-GBM antibody in glomerular basement membrane can be measured by the ELISA assay. In addition, the recombinant rat antigen is secreted in HEK293 cell supernatant which is purified by Anti-FLAG M2 monoclonal IgG antibody affinity column. In addition, it is characterized and quantified by SDS-PAGE gel electrophoresis and Western blotting techniques.

scholarly journals Monotypic IgG1-kappa Atypical Anti-Glomerular Basement Membrane Nephritis: A Case Report

2019 ◽  
Vol 9 (1) ◽  
pp. 8-14
Author(s):  
Maxim Olivier ◽  
Harold Watson ◽  
Danielle Lee ◽  
Viresh Mohanlal ◽  
Mario Madruga ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Basement Membrane ◽  
Renal Biopsy ◽  
Glomerular Basement Membrane ◽  
Hemorrhagic Cystitis ◽  
Oral Cyclophosphamide ◽  
First Line ◽  
Circulating Autoantibodies ◽  
Line Drug ◽  
Observation Period

Anti-glomerular basement membrane (anti-GBM) glomerulonephritis is a rare disease caused by autoantibodies against the glomerular basement membrane. Atypical anti-GBM nephritis is clinically less aggressive and characterized by the absence of circulating autoantibodies to the basement membrane. A previously healthy 53-year-old white woman presented with a rising creatinine over a short observation period. Renal biopsy, urinary sediment, and laboratory testing confirmed the diagnosis of atypical anti-GBM disease. She received plasmapheresis, steroids, and cyclophosphamide. She developed hemorrhagic cystitis early in the treatment from oral cyclophosphamide and mycophenolate mofetil was substituted as a first-line drug. She responded favorably and continued on mycophenolate mofetil without evidence of relapse. Despite the absence of circulating autoantibodies, a diagnosis of atypical anti-GBM nephritis should not be excluded if a high index of clinical suspicion exists. Early renal biopsy should be considered. Mycophenolate mofetil may be a reasonable replacement for oral cyclophosphamide in the treatment of atypical anti-GBM disease when cyclophosphamide is contraindicated.

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