Variability of the Antigenicity of the Glomerular Basement Membrane in 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 LMX1B 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 LMX1B gene, which may account for the disrupted GBM structure. Further studies are warranted to elucidate the complex genotype-phenotype relationship between LMX1B and proper GBM morphogenesis.

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

Nature Genetics ◽

10.1038/84853 ◽

2001 ◽

Vol 27 (2) ◽

pp. 205-208 ◽

Cited By ~ 142

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

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Thin glomerular basement membrane nephropathy and other collagenopathies

10.1093/med/9780199592548.003.0325_update_001 ◽

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.

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An autosomal recessive disorder with glomerular basement membrane abnormalities similar to those seen in the nail patella syndrome: Report of a kindred

American Journal of Medical Genetics ◽

10.1002/ajmg.1320190321 ◽

1984 ◽

Vol 19 (3) ◽

pp. 579-584 ◽

Cited By ~ 30

Author(s):

Jose R. Salcedo

Keyword(s):

Basement Membrane ◽

Glomerular Basement Membrane ◽

Autosomal Recessive ◽

Autosomal Recessive Disorder ◽

Nail Patella Syndrome ◽

Syndrome Report

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Electron microscopic radioautographic studies on the incorporation of 3H proline in the glomerular basement membrane (GBM) in antistreptococcal-cell-membrane (SCM) injected mice

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100111057 ◽

1984 ◽

Vol 42 ◽

pp. 188-189

Author(s):

R.P. Nayyar ◽

C.F. Lange ◽

J. L. Borke

Keyword(s):

Body Weight ◽

Cell Membrane ◽

Basement Membrane ◽

Glomerular Basement Membrane ◽

Mesangial Matrix ◽

Electron Microscopic ◽

Group A ◽

Injection Protocol

Streptococcal cell membrane (SCM) antiserum injected mice show a significant thickening of glomerular basement membrane (GBM) and an increase in mesangial matrix within 4 to 24 hours of antiserum administration (1,2,3). This study was undertaken to evaluate the incorporation of 3H proline into glomerular cells and GBM under normal and anti-SCM induced conditions. Mice were administered, intraperitoneally, 0.1 ml of normal or anti-SCM serum followed by a 10 µC/g body weight injection of 3H proline. Details of the preparation of anti-SCM (Group A type 12 streptococcal pyogenes) and other sera and injection protocol have been described elsewhere (2). After 15 minutes of isotope injection a chase of cold proline was given and animal sacrificed at 20 minutes, 1,2,4,8,24 and 48 hours. One of the removed kidneys was processed for immunofluorescence, light and electron microscopic radioautographic studies; second kidney was used for GBM isolation and aminoacid analysis.

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