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A Unique Genotype of Pseudohypoaldosteronism Type 1b in a Highly Consanguineous Population

CONTEXT: Pseudohypoaldosteronism (PHA) is a condition in which serum aldosterone level is normal or elevated but its action is deficient. OBJECTIVE: This study describes the molecular genetics of PHA 1b in the highly consanguineous population of 2 Arabian Gulf countries, Saudi Arabia and Oman. METHO...

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Autores principales: Alzahrani, Ali S, Alswailem, Meshael, Abbas, Bassam Bin, Qasem, Ebtesam, Alsagheir, Afaf, Al Shidhani, Azza, Al Sinani, Aisha, Al Badi, Maryam, Al-Maqbali, Ali, Al Shawi, Manal, Albunyan, Abdulhameed, Bin Nafisah, Abdulghani, Shi, Yufei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272535/
https://www.ncbi.nlm.nih.gov/pubmed/34258491
http://dx.doi.org/10.1210/jendso/bvab095
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author Alzahrani, Ali S
Alswailem, Meshael
Abbas, Bassam Bin
Qasem, Ebtesam
Alsagheir, Afaf
Al Shidhani, Azza
Al Sinani, Aisha
Al Badi, Maryam
Al-Maqbali, Ali
Al Shawi, Manal
Albunyan, Abdulhameed
Bin Nafisah, Abdulghani
Shi, Yufei
author_facet Alzahrani, Ali S
Alswailem, Meshael
Abbas, Bassam Bin
Qasem, Ebtesam
Alsagheir, Afaf
Al Shidhani, Azza
Al Sinani, Aisha
Al Badi, Maryam
Al-Maqbali, Ali
Al Shawi, Manal
Albunyan, Abdulhameed
Bin Nafisah, Abdulghani
Shi, Yufei
author_sort Alzahrani, Ali S
collection PubMed
description CONTEXT: Pseudohypoaldosteronism (PHA) is a condition in which serum aldosterone level is normal or elevated but its action is deficient. OBJECTIVE: This study describes the molecular genetics of PHA 1b in the highly consanguineous population of 2 Arabian Gulf countries, Saudi Arabia and Oman. METHODS: This study enrolled 22 patients from 13 unrelated families (2 families with 5 patients from Oman and 11 families with 17 patients from Saudi Arabia). All of these patients had presented within the first 10 days of life with nausea and vomiting, hyponatremia, hyperkalemia, and hypotension. We isolated DNA from peripheral blood and PCR-sequenced all exons and exon-intron boundaries of SCNN1A and, if negative, SCNN1B and SCNN1G using the Dideoxy Chain termination method. RESULTS: We found a total of 8 mutations in 13 families as follows: 6 mutations in SCNN1A, 1 in SCNN1B, and 1 in SCNN1G. All of these mutations were novel except one. SCNN1A mutations were: c.1496A>G, p.Q499R (novel) in 1 patient; c.1453C>T, p.Q485X (novel) in 1 patient; c.1322_1322delA, p.N441Tfs*41 (novel) in 2 patients of 1 family; c.876 + 2 delGAGT (novel) in 3 patients of 1 family; c.203_204 delTC, p.I68Tfs*76 (a known mutation) in 8 patients of 5 families; and whole SCNN1A gene deletion (novel) in 2 patients of 2 families. In addition, a nonsense SCNN1B mutation c.1694C>A, p.S565X (novel) was found in 3 siblings from 1 Omani family, and an SCNN1G deletion mutation c.527_528 delCA, p.T176Rfs*9 (novel) in 2 siblings from another Omani family. CONCLUSION: We characterized a unique genotype of PHA 1b with several novel gene structure–disrupting mutations in SCNN1A, SCNN1B, and SCNN1G in a highly consanguineous population.
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spelling pubmed-82725352021-07-12 A Unique Genotype of Pseudohypoaldosteronism Type 1b in a Highly Consanguineous Population Alzahrani, Ali S Alswailem, Meshael Abbas, Bassam Bin Qasem, Ebtesam Alsagheir, Afaf Al Shidhani, Azza Al Sinani, Aisha Al Badi, Maryam Al-Maqbali, Ali Al Shawi, Manal Albunyan, Abdulhameed Bin Nafisah, Abdulghani Shi, Yufei J Endocr Soc Clinical Research Articles CONTEXT: Pseudohypoaldosteronism (PHA) is a condition in which serum aldosterone level is normal or elevated but its action is deficient. OBJECTIVE: This study describes the molecular genetics of PHA 1b in the highly consanguineous population of 2 Arabian Gulf countries, Saudi Arabia and Oman. METHODS: This study enrolled 22 patients from 13 unrelated families (2 families with 5 patients from Oman and 11 families with 17 patients from Saudi Arabia). All of these patients had presented within the first 10 days of life with nausea and vomiting, hyponatremia, hyperkalemia, and hypotension. We isolated DNA from peripheral blood and PCR-sequenced all exons and exon-intron boundaries of SCNN1A and, if negative, SCNN1B and SCNN1G using the Dideoxy Chain termination method. RESULTS: We found a total of 8 mutations in 13 families as follows: 6 mutations in SCNN1A, 1 in SCNN1B, and 1 in SCNN1G. All of these mutations were novel except one. SCNN1A mutations were: c.1496A>G, p.Q499R (novel) in 1 patient; c.1453C>T, p.Q485X (novel) in 1 patient; c.1322_1322delA, p.N441Tfs*41 (novel) in 2 patients of 1 family; c.876 + 2 delGAGT (novel) in 3 patients of 1 family; c.203_204 delTC, p.I68Tfs*76 (a known mutation) in 8 patients of 5 families; and whole SCNN1A gene deletion (novel) in 2 patients of 2 families. In addition, a nonsense SCNN1B mutation c.1694C>A, p.S565X (novel) was found in 3 siblings from 1 Omani family, and an SCNN1G deletion mutation c.527_528 delCA, p.T176Rfs*9 (novel) in 2 siblings from another Omani family. CONCLUSION: We characterized a unique genotype of PHA 1b with several novel gene structure–disrupting mutations in SCNN1A, SCNN1B, and SCNN1G in a highly consanguineous population. Oxford University Press 2021-05-17 /pmc/articles/PMC8272535/ /pubmed/34258491 http://dx.doi.org/10.1210/jendso/bvab095 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Clinical Research Articles
Alzahrani, Ali S
Alswailem, Meshael
Abbas, Bassam Bin
Qasem, Ebtesam
Alsagheir, Afaf
Al Shidhani, Azza
Al Sinani, Aisha
Al Badi, Maryam
Al-Maqbali, Ali
Al Shawi, Manal
Albunyan, Abdulhameed
Bin Nafisah, Abdulghani
Shi, Yufei
A Unique Genotype of Pseudohypoaldosteronism Type 1b in a Highly Consanguineous Population
title A Unique Genotype of Pseudohypoaldosteronism Type 1b in a Highly Consanguineous Population
title_full A Unique Genotype of Pseudohypoaldosteronism Type 1b in a Highly Consanguineous Population
title_fullStr A Unique Genotype of Pseudohypoaldosteronism Type 1b in a Highly Consanguineous Population
title_full_unstemmed A Unique Genotype of Pseudohypoaldosteronism Type 1b in a Highly Consanguineous Population
title_short A Unique Genotype of Pseudohypoaldosteronism Type 1b in a Highly Consanguineous Population
title_sort unique genotype of pseudohypoaldosteronism type 1b in a highly consanguineous population
topic Clinical Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272535/
https://www.ncbi.nlm.nih.gov/pubmed/34258491
http://dx.doi.org/10.1210/jendso/bvab095
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