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
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.
J Endocr Soc. 2021 May 17;5(8):bvab095. doi: 10.1210/jendso/bvab095. eCollection 2021 Aug 1.
Pseudohypoaldosteronism (PHA) is a condition in which serum aldosterone level is normal or elevated but its action is deficient.
This study describes the molecular genetics of PHA 1b in the highly consanguineous population of 2 Arabian Gulf countries, Saudi Arabia and Oman.
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 and, if negative, and using the Dideoxy Chain termination method.
We found a total of 8 mutations in 13 families as follows: 6 mutations in , 1 in , and 1 in . All of these mutations were novel except one. mutations were: c.1496A>G, p.Q499R (novel) in 1 patient; c.1453C>T, p.Q485X (novel) in 1 patient; c.1322_1322delA, p.N441Tfs41 (novel) in 2 patients of 1 family; c.876 + 2 delGAGT (novel) in 3 patients of 1 family; c.203_204 delTC, p.I68Tfs76 (a known mutation) in 8 patients of 5 families; and whole gene deletion (novel) in 2 patients of 2 families. In addition, a nonsense mutation c.1694C>A, p.S565X (novel) was found in 3 siblings from 1 Omani family, and an deletion mutation c.527_528 delCA, p.T176Rfs*9 (novel) in 2 siblings from another Omani family.
We characterized a unique genotype of PHA 1b with several novel gene structure-disrupting mutations in , , and in a highly consanguineous population.
假性醛固酮增多症（PHA）是一种血清醛固酮水平正常或升高但其作用不足的病症。
本研究描述了沙特阿拉伯和阿曼这两个阿拉伯海湾国家高度近亲通婚人群中1b型PHA的分子遗传学特征。
本研究纳入了来自13个无亲缘关系家庭的22例患者（2个家庭共5例患者来自阿曼，11个家庭共17例患者来自沙特阿拉伯）。所有这些患者在出生后的前10天内均出现恶心、呕吐、低钠血症、高钾血症和低血压症状。我们从外周血中提取DNA，并使用双脱氧链终止法对 、 （若 检测为阴性则检测 ）以及 （若 检测为阴性则检测 ）的所有外显子和外显子 - 内含子边界进行PCR测序。
我们在13个家庭中总共发现了如下8个突变： 在 中有6个突变， 在 中有1个突变， 在 中有1个突变。除1个突变外，所有这些突变均为新发现的突变。 在 中的突变有：1例患者中为c.1496A>G，p.Q499R（新发现）；1例患者中为c.1453C>T，p.Q485X（新发现）；1个家庭的2例患者中为c.1322_1322delA，p.N441Tfs41（新发现）；1个家庭的3例患者中为c.876 + 2 delGAGT（新发现）；5个家庭的8例患者中为c.203_204 delTC，p.I68Tfs76（已知突变）；2个家庭的2例患者中为整个 基因缺失（新发现）。此外，在1个阿曼家庭的3名同胞中发现了1个无义突变c.1694C>A，p.S565X（新发现），在另1个阿曼家庭的2名同胞中发现了1个 缺失突变c.527_528 delCA，p.T176Rfs*9（新发现）。
我们在一个高度近亲通婚人群中鉴定出了1b型PHA的独特基因型，其中 、 和 存在多个新发现的破坏基因结构的突变。
