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A novel missense mutation in GREB1L identified in a three-generation family with renal hypodysplasia/aplasia-3
BACKGROUND: Renal hypodysplasia/aplasia-3 (RHDA3), as the most severe end of the spectrum of congenital anomalies of the kidney and urinary tract, is mainly caused by mutations in GREB1L. However, the mutations in GREB1L identified to date only explain a limited proportion of RHDA3 cases, and the me...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9652819/ https://www.ncbi.nlm.nih.gov/pubmed/36371238 http://dx.doi.org/10.1186/s13023-022-02553-w |
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author | Wu, Sixian Wang, Xiang Dai, Siyu Zhang, Guohui Zhou, Jiaojiao Shen, Ying |
author_facet | Wu, Sixian Wang, Xiang Dai, Siyu Zhang, Guohui Zhou, Jiaojiao Shen, Ying |
author_sort | Wu, Sixian |
collection | PubMed |
description | BACKGROUND: Renal hypodysplasia/aplasia-3 (RHDA3), as the most severe end of the spectrum of congenital anomalies of the kidney and urinary tract, is mainly caused by mutations in GREB1L. However, the mutations in GREB1L identified to date only explain a limited proportion of RHDA3 cases, and the mechanism of GREB1L mutations causing RHDA3 is unclear. RESULTS: According to whole-exome sequencing, a three-generation family suffering from RHDA3 was investigated with a novel missense mutation in GREB1L, c.4507C>T. All three-generation patients suffered from unilateral absent kidney. This missense mutation resulted in sharp downregulation of mRNA and protein expression, which might lead to RHDA3. Mechanistically, through RNA-sequencing, it was found that the mRNA levels of PAX2 and PTH1R, which are key molecules involved in the development of the kidney, were significantly downregulated by knocking out GREB1L in vitro. CONCLUSIONS: This novel missense mutation in GREB1L can be helpful in the genetic diagnosis of RHDA3, and the discovery of the potential mechanism that GREB1L mutations involved in RHDA3 pathogenesis can promote the adoption of optimal treatment measures and the development of personalized medicine directly targeting these effects. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-022-02553-w. |
format | Online Article Text |
id | pubmed-9652819 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-96528192022-11-15 A novel missense mutation in GREB1L identified in a three-generation family with renal hypodysplasia/aplasia-3 Wu, Sixian Wang, Xiang Dai, Siyu Zhang, Guohui Zhou, Jiaojiao Shen, Ying Orphanet J Rare Dis Research BACKGROUND: Renal hypodysplasia/aplasia-3 (RHDA3), as the most severe end of the spectrum of congenital anomalies of the kidney and urinary tract, is mainly caused by mutations in GREB1L. However, the mutations in GREB1L identified to date only explain a limited proportion of RHDA3 cases, and the mechanism of GREB1L mutations causing RHDA3 is unclear. RESULTS: According to whole-exome sequencing, a three-generation family suffering from RHDA3 was investigated with a novel missense mutation in GREB1L, c.4507C>T. All three-generation patients suffered from unilateral absent kidney. This missense mutation resulted in sharp downregulation of mRNA and protein expression, which might lead to RHDA3. Mechanistically, through RNA-sequencing, it was found that the mRNA levels of PAX2 and PTH1R, which are key molecules involved in the development of the kidney, were significantly downregulated by knocking out GREB1L in vitro. CONCLUSIONS: This novel missense mutation in GREB1L can be helpful in the genetic diagnosis of RHDA3, and the discovery of the potential mechanism that GREB1L mutations involved in RHDA3 pathogenesis can promote the adoption of optimal treatment measures and the development of personalized medicine directly targeting these effects. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-022-02553-w. BioMed Central 2022-11-12 /pmc/articles/PMC9652819/ /pubmed/36371238 http://dx.doi.org/10.1186/s13023-022-02553-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Wu, Sixian Wang, Xiang Dai, Siyu Zhang, Guohui Zhou, Jiaojiao Shen, Ying A novel missense mutation in GREB1L identified in a three-generation family with renal hypodysplasia/aplasia-3 |
title | A novel missense mutation in GREB1L identified in a three-generation family with renal hypodysplasia/aplasia-3 |
title_full | A novel missense mutation in GREB1L identified in a three-generation family with renal hypodysplasia/aplasia-3 |
title_fullStr | A novel missense mutation in GREB1L identified in a three-generation family with renal hypodysplasia/aplasia-3 |
title_full_unstemmed | A novel missense mutation in GREB1L identified in a three-generation family with renal hypodysplasia/aplasia-3 |
title_short | A novel missense mutation in GREB1L identified in a three-generation family with renal hypodysplasia/aplasia-3 |
title_sort | novel missense mutation in greb1l identified in a three-generation family with renal hypodysplasia/aplasia-3 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9652819/ https://www.ncbi.nlm.nih.gov/pubmed/36371238 http://dx.doi.org/10.1186/s13023-022-02553-w |
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