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Mutation Analysis of Thin Basement Membrane Nephropathy

Thin basement membrane nephropathy (TBMN) is characterized by the observation of microhematuria and a thin glomerular basement membrane on kidney biopsy specimens. Its main cause is heterozygous mutations of COL4A3 or COL4A4, which also cause late-onset focal segmental glomerulosclerosis (FSGS) or a...

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Autores principales: Hirabayashi, Yosuke, Katayama, Kan, Mori, Mutsuki, Matsuo, Hiroshi, Fujimoto, Mika, Joh, Kensuke, Murata, Tomohiro, Ito, Masaaki, Dohi, Kaoru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9602179/
https://www.ncbi.nlm.nih.gov/pubmed/36292665
http://dx.doi.org/10.3390/genes13101779
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author Hirabayashi, Yosuke
Katayama, Kan
Mori, Mutsuki
Matsuo, Hiroshi
Fujimoto, Mika
Joh, Kensuke
Murata, Tomohiro
Ito, Masaaki
Dohi, Kaoru
author_facet Hirabayashi, Yosuke
Katayama, Kan
Mori, Mutsuki
Matsuo, Hiroshi
Fujimoto, Mika
Joh, Kensuke
Murata, Tomohiro
Ito, Masaaki
Dohi, Kaoru
author_sort Hirabayashi, Yosuke
collection PubMed
description Thin basement membrane nephropathy (TBMN) is characterized by the observation of microhematuria and a thin glomerular basement membrane on kidney biopsy specimens. Its main cause is heterozygous mutations of COL4A3 or COL4A4, which also cause late-onset focal segmental glomerulosclerosis (FSGS) or autosomal dominant Alport syndrome (ADAS). Thirteen TBMN cases were analyzed using Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and exome sequencing. Ten heterozygous variants were detected in COL4A3 or COL4A4 in nine patients via Sanger sequencing, three of which were novel variants. The diagnostic rate of “likely pathogenic” or “pathogenic” under the American College of Medical Genetics and Genomics guidelines was 53.8% (7 out of 13 patients). There were eight single nucleotide variants, seven of which were glycine substitutions in the collagenous domain, one of which was a splice-site single nucleotide variant, and two of which were deletion variants. One patient had digenic variants in COL4A3 and COL4A4. While MLPA analyses showed negative results, exome sequencing identified three heterozygous variants in causative genes of FSGS in four patients with no apparent variants on Sanger sequencing. Since patients with heterozygous mutations of COL4A3 or COL4A4 showed a wide spectrum of disease from TBMN to ADAS, careful follow-up will be necessary for these patients.
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spelling pubmed-96021792022-10-27 Mutation Analysis of Thin Basement Membrane Nephropathy Hirabayashi, Yosuke Katayama, Kan Mori, Mutsuki Matsuo, Hiroshi Fujimoto, Mika Joh, Kensuke Murata, Tomohiro Ito, Masaaki Dohi, Kaoru Genes (Basel) Article Thin basement membrane nephropathy (TBMN) is characterized by the observation of microhematuria and a thin glomerular basement membrane on kidney biopsy specimens. Its main cause is heterozygous mutations of COL4A3 or COL4A4, which also cause late-onset focal segmental glomerulosclerosis (FSGS) or autosomal dominant Alport syndrome (ADAS). Thirteen TBMN cases were analyzed using Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and exome sequencing. Ten heterozygous variants were detected in COL4A3 or COL4A4 in nine patients via Sanger sequencing, three of which were novel variants. The diagnostic rate of “likely pathogenic” or “pathogenic” under the American College of Medical Genetics and Genomics guidelines was 53.8% (7 out of 13 patients). There were eight single nucleotide variants, seven of which were glycine substitutions in the collagenous domain, one of which was a splice-site single nucleotide variant, and two of which were deletion variants. One patient had digenic variants in COL4A3 and COL4A4. While MLPA analyses showed negative results, exome sequencing identified three heterozygous variants in causative genes of FSGS in four patients with no apparent variants on Sanger sequencing. Since patients with heterozygous mutations of COL4A3 or COL4A4 showed a wide spectrum of disease from TBMN to ADAS, careful follow-up will be necessary for these patients. MDPI 2022-10-02 /pmc/articles/PMC9602179/ /pubmed/36292665 http://dx.doi.org/10.3390/genes13101779 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hirabayashi, Yosuke
Katayama, Kan
Mori, Mutsuki
Matsuo, Hiroshi
Fujimoto, Mika
Joh, Kensuke
Murata, Tomohiro
Ito, Masaaki
Dohi, Kaoru
Mutation Analysis of Thin Basement Membrane Nephropathy
title Mutation Analysis of Thin Basement Membrane Nephropathy
title_full Mutation Analysis of Thin Basement Membrane Nephropathy
title_fullStr Mutation Analysis of Thin Basement Membrane Nephropathy
title_full_unstemmed Mutation Analysis of Thin Basement Membrane Nephropathy
title_short Mutation Analysis of Thin Basement Membrane Nephropathy
title_sort mutation analysis of thin basement membrane nephropathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9602179/
https://www.ncbi.nlm.nih.gov/pubmed/36292665
http://dx.doi.org/10.3390/genes13101779
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