A Unique Genotype of Pseudohypoaldosteronism Type 1b in a Highly Consanguineous Population.
| Autor: | Alzahrani AS; Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia.; Department of Molecular Oncology, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia., Alswailem M; Department of Molecular Oncology, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia., Abbas BB; Department of Pediatrics, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia., Qasem E; Department of Molecular Oncology, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia., Alsagheir A; Department of Pediatrics, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia., Al Shidhani A; Department of Pediatrics, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia., Al Sinani A; Department of Pediatrics, Royal Hospital, 111 Muscat, Oman., Al Badi M; Department of Pediatrics, Royal Hospital, 111 Muscat, Oman., Al-Maqbali A; Department of Medicine, Royal Hospital 111, Muscat, Oman., Al Shawi M; Maternity and Children Hospital, Alhasa 36361, Saudi Arabia., Albunyan A; Maternity and Children Hospital, Alhasa 36361, Saudi Arabia., Bin Nafisah A; Department of Molecular Oncology, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia., Shi Y; Center for Genomic Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of the Endocrine Society [J Endocr Soc] 2021 May 17; Vol. 5 (8), pp. bvab095. Date of Electronic Publication: 2021 May 17 (Print Publication: 2021). |
| DOI: | 10.1210/jendso/bvab095 |
| Abstrakt: | 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. (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.) |
| Databáze: | MEDLINE |
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