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Autosomal dominant pseudohypoaldosteronism type 1 with a novel splice site mutation in MR gene

BACKGROUND: Autosomal dominant pseudohypoaldosteronism type 1 (PHA1) is a rare inherited condition that is characterized by renal resistance to aldosterone as well as salt wasting, hyperkalemia, and metabolic acidosis. Renal PHA1 is caused by mutations of the human mineralcorticoid receptor gene (MR...

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Autores principales: Kanda, Kyoko, Nozu, Kandai, Yokoyama, Naoki, Morioka, Ichiro, Miwa, Akihiro, Hashimura, Yuya, Kaito, Hiroshi, Iijima, Kazumoto, Matsuo, Masafumi
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779785/
https://www.ncbi.nlm.nih.gov/pubmed/19912655
http://dx.doi.org/10.1186/1471-2369-10-37
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author Kanda, Kyoko
Nozu, Kandai
Yokoyama, Naoki
Morioka, Ichiro
Miwa, Akihiro
Hashimura, Yuya
Kaito, Hiroshi
Iijima, Kazumoto
Matsuo, Masafumi
author_facet Kanda, Kyoko
Nozu, Kandai
Yokoyama, Naoki
Morioka, Ichiro
Miwa, Akihiro
Hashimura, Yuya
Kaito, Hiroshi
Iijima, Kazumoto
Matsuo, Masafumi
author_sort Kanda, Kyoko
collection PubMed
description BACKGROUND: Autosomal dominant pseudohypoaldosteronism type 1 (PHA1) is a rare inherited condition that is characterized by renal resistance to aldosterone as well as salt wasting, hyperkalemia, and metabolic acidosis. Renal PHA1 is caused by mutations of the human mineralcorticoid receptor gene (MR), but it is a matter of debate whether MR mutations cause mineralcorticoid resistance via haploinsufficiency or dominant negative mechanism. It was previously reported that in a case with nonsense mutation the mutant mRNA was absent in lymphocytes because of nonsense mediated mRNA decay (NMD) and therefore postulated that haploinsufficiency alone can give rise to the PHA1 phenotype in patients with truncated mutations. METHODS AND RESULTS: We conducted genomic DNA analysis and mRNA analysis for familial PHA1 patients extracted from lymphocytes and urinary sediments and could detect one novel splice site mutation which leads to exon skipping and frame shift result in premature termination at the transcript level. The mRNA analysis showed evidence of wild type and exon-skipped RT-PCR products. CONCLUSION: mRNA analysis have been rarely conducted for PHA1 because kidney tissues are unavailable for this disease. However, we conducted RT-PCR analysis using mRNA extracted from urinary sediments. We could demonstrate that NMD does not fully function in kidney cells and that haploinsufficiency due to NMD with premature termination is not sufficient to give rise to the PHA1 phenotype at least in this mutation of our patient. Additional studies including mRNA analysis will be needed to identify the exact mechanism of the phenotype of PHA.
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spelling pubmed-27797852009-11-20 Autosomal dominant pseudohypoaldosteronism type 1 with a novel splice site mutation in MR gene Kanda, Kyoko Nozu, Kandai Yokoyama, Naoki Morioka, Ichiro Miwa, Akihiro Hashimura, Yuya Kaito, Hiroshi Iijima, Kazumoto Matsuo, Masafumi BMC Nephrol Research Article BACKGROUND: Autosomal dominant pseudohypoaldosteronism type 1 (PHA1) is a rare inherited condition that is characterized by renal resistance to aldosterone as well as salt wasting, hyperkalemia, and metabolic acidosis. Renal PHA1 is caused by mutations of the human mineralcorticoid receptor gene (MR), but it is a matter of debate whether MR mutations cause mineralcorticoid resistance via haploinsufficiency or dominant negative mechanism. It was previously reported that in a case with nonsense mutation the mutant mRNA was absent in lymphocytes because of nonsense mediated mRNA decay (NMD) and therefore postulated that haploinsufficiency alone can give rise to the PHA1 phenotype in patients with truncated mutations. METHODS AND RESULTS: We conducted genomic DNA analysis and mRNA analysis for familial PHA1 patients extracted from lymphocytes and urinary sediments and could detect one novel splice site mutation which leads to exon skipping and frame shift result in premature termination at the transcript level. The mRNA analysis showed evidence of wild type and exon-skipped RT-PCR products. CONCLUSION: mRNA analysis have been rarely conducted for PHA1 because kidney tissues are unavailable for this disease. However, we conducted RT-PCR analysis using mRNA extracted from urinary sediments. We could demonstrate that NMD does not fully function in kidney cells and that haploinsufficiency due to NMD with premature termination is not sufficient to give rise to the PHA1 phenotype at least in this mutation of our patient. Additional studies including mRNA analysis will be needed to identify the exact mechanism of the phenotype of PHA. BioMed Central 2009-11-14 /pmc/articles/PMC2779785/ /pubmed/19912655 http://dx.doi.org/10.1186/1471-2369-10-37 Text en Copyright ©2009 Kanda et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kanda, Kyoko
Nozu, Kandai
Yokoyama, Naoki
Morioka, Ichiro
Miwa, Akihiro
Hashimura, Yuya
Kaito, Hiroshi
Iijima, Kazumoto
Matsuo, Masafumi
Autosomal dominant pseudohypoaldosteronism type 1 with a novel splice site mutation in MR gene
title Autosomal dominant pseudohypoaldosteronism type 1 with a novel splice site mutation in MR gene
title_full Autosomal dominant pseudohypoaldosteronism type 1 with a novel splice site mutation in MR gene
title_fullStr Autosomal dominant pseudohypoaldosteronism type 1 with a novel splice site mutation in MR gene
title_full_unstemmed Autosomal dominant pseudohypoaldosteronism type 1 with a novel splice site mutation in MR gene
title_short Autosomal dominant pseudohypoaldosteronism type 1 with a novel splice site mutation in MR gene
title_sort autosomal dominant pseudohypoaldosteronism type 1 with a novel splice site mutation in mr gene
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779785/
https://www.ncbi.nlm.nih.gov/pubmed/19912655
http://dx.doi.org/10.1186/1471-2369-10-37
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