Aldosterone synthase deficiency (ASD) is a rare potentially life‐threatening genetic disorder that usually presents during infancy due to pathogenic variants in the CYP11B2 gene. Knowledge about CYP11B2 variants in the Arab population is scarce. Here, we present and analyze five Palestinian patients and their different novel pathogenic variants. Data on clinical presentation, electrolytes, plasma renin activity, and steroid hormone levels of five patients diagnosed with ASD were summarized. Sequencing of the CYP11B2 gene exons was followed by evolutionary conservation analysis and structural modeling of the variants. All patients were from highly consanguineous Palestinian families. The patients presented at 1–4 months of age with recurrent vomiting, poor weight gain, hyponatremia, hyperkalemia, and low aldosterone levels. Genetic analysis of the CYP11B2 gene revealed three homozygous pathogenic variants: p.Ser344Profs*9, p.G452W in two patients from an extended family, and p.Q338stop. A previously described pathogenic variant was found in one patient: p.G288S. We described four different CYP11B2 gene pathogenic variants in a relatively small population. Our findings may contribute to the future early diagnosis and therapy for patients with ASD among Arab patients who present with failure to thrive and compatible electrolyte disturbances.

中文翻译：

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巴勒斯坦婴儿醛固酮合酶 (CYP11B2) 缺乏症：三种新变异和遗传异质性

醛固酮合酶缺乏症 (ASD) 是一种罕见的可能危及生命的遗传疾病，通常在婴儿期由于 CYP11B2 基因的致病变异而出现。关于阿拉伯人群中 CYP11B2 变异的知识很少。在这里，我们介绍并分析了五名巴勒斯坦患者及其不同的新型致病变异。总结了五名诊断为 ASD 的患者的临床表现、电解质、血浆肾素活性和类固醇激素水平的数据。CYP11B2 基因外显子的测序之后是进化保守性分析和变体的结构建模。所有患者均来自血缘关系密切的巴勒斯坦家庭。患者在 1-4 个月大时出现反复呕吐、体重增加缓慢、低钠血症、高钾血症和低醛固酮水平。CYP11B2 基因的遗传分析揭示了三个纯合的致病变异：p.Ser344Profs*9、来自一个大家族的两名患者的 p.G452W 和 p.Q338stop。在一名患者中发现了先前描述的致病性变异：p.G288S。我们在相对较小的人群中描述了四种不同的 CYP11B2 基因致病变异。我们的研究结果可能有助于未来对 ASD 患者的早期诊断和治疗，这些阿拉伯患者表现为生长发育迟缓和电解质紊乱。