TY - JOUR
T1 - A Unique Genotype of Pseudohypoaldosteronism Type 1b in a Highly Consanguineous Population
AU - Al-Shidhani, Azza
N1 - Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - ENaC
KW - PHA
KW - SCNN1A
KW - SCNN1B
KW - SCNN1G
KW - pseudohypoaldosteronism
KW - sodium epithelial channel
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U2 - 10.1210/jendso/bvab095
DO - 10.1210/jendso/bvab095
M3 - Article
SN - 2472-1972
VL - 5
JO - Journal of the Endocrine Society
JF - Journal of the Endocrine Society
IS - 8
M1 - bvab095
ER -