A Novel LMX1B Variant Identified in a Patient Presenting with Severe Renal Involvement and Thin Glomerular Basement Membrane-Reference-Cited by-同舟云学术

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

Published:2021 Issue:6 Volume:145 Page:776-782
ISSN:1660-8151
Container-title:Nephron
language:en
Short-container-title:Nephron

Author:

Morimoto Nobuhisa,Nagahama Kiyotaka,Mori Takayasu,Fujimaru Takuya^ORCID,Tsuura Yukio,Terai Ayumi,Tanabe Madoka,Otani Megumi,Shioji Shingo,Hirasawa Suguru,Aki Shota,Aoyagi Makoto,Sohara Eisei,Uchida Shinichi,Tanaka Hiroyuki

Abstract

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.

Publisher

S. Karger AG

Reference33 articles.

1. Dreyer SD, Zhou G, Baldini A, Winterpacht A, Zabel B, Cole W, et al. Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome. Nat Genet. 1998 May;19(1):47–50.

2. McIntosh I, Dreyer SD, Clough MV, Dunston JA, Eyaid W, Roig CM, et al. Mutation analysis of LMX1B gene in nail-patella syndrome patients. Am J Hum Genet. 1998 Dec;63(6):1651–8.

3. Vollrath D, Jaramillo-Babb VL, Clough MV, McIntosh I, Scott KM, Lichter PR, et al. Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome. Hum Mol Genet. 1998 July;7(7):1091–8.

4. Rohr C, Prestel J, Heidet L, Hosser H, Kriz W, Johnson RL, et al. The LIM-homeodomain transcription factor Lmx1b plays a crucial role in podocytes. J Clin Invest. 2002 Apr;109(8):1073–82.

5. Bongers EM, Huysmans FT, Levtchenko E, de Rooy JW, Blickman JG, Admiraal RJ, et al. Genotype-phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy. Eur J Hum Genet. 2005 Aug;13(8):935–46.