Severe aldosterone synthase deficiency in a nine-day old Lebanese boy: the importance of functional studies to establish pathogenicity of seemingly benign variants in CYP11B2.

IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Chiraz Ghaddhab, Cameron C Capper, Stéphanie Larrivée-Vanier, Wissam Fayad, Patricia Olivier, Guy Van Vliet, Richard J Auchus, Johnny Deladoëy
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引用次数: 0

Abstract

Introduction Aldosterone synthase deficiency is a rare autosomal recessive disease characterized by vomiting, dehydration, salt wasting, life-threatening hyperkalemia in infancy, followed by failure to thrive. It results from pathogenic variants in CYP11B2. Case Presentation A boy, born in Montreal to Lebanese parents who are first cousins, was referred at nine days of life for severe dehydration. A diagnosis of primary adrenal insufficiency was made, and treatment was started with fludrocortisone and hydrocortisone. Exome sequencing revealed a homozygous variant p.(Asn201Asp)(N201D). In silico, this variant was considered benign, but in vitro functional expression studies established it caused the severe aldosterone deficiency. It ended the diagnostic odyssey and allowed to safely stop hydrocortisone replacement. Conclusion If a gene variant co-segregates with a phenotype, in vitro functional studies are required even if in silico studies are negative.

一名九天大的黎巴嫩男孩患有严重的醛固酮合成酶缺乏症:功能研究对于确定 CYP11B2 中看似良性变体的致病性非常重要。
导言醛固酮合成酶缺乏症是一种罕见的常染色体隐性遗传病,其特征是婴儿期呕吐、脱水、盐耗竭和危及生命的高钾血症,随后发育不良。它是由 CYP11B2 的致病变体引起的。病例介绍 一名出生在蒙特利尔的男孩,父母是黎巴嫩人,他们是嫡亲表兄弟。诊断结果为原发性肾上腺功能不全,并开始使用氟氢可的松和氢化可的松进行治疗。外显子组测序发现了一个同源变异 p.(Asn201Asp)(N201D)。该变异被认为是良性的,但体外功能表达研究证实它导致了严重的醛固酮缺乏症。诊断工作就此结束,可以安全地停止氢化可的松替代治疗。结论 如果基因变异与表型共分离,即使硅学研究结果为阴性,也需要进行体外功能研究。
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来源期刊
Hormone Research in Paediatrics
Hormone Research in Paediatrics ENDOCRINOLOGY & METABOLISM-PEDIATRICS
CiteScore
4.90
自引率
6.20%
发文量
88
审稿时长
4-8 weeks
期刊介绍: The mission of ''Hormone Research in Paediatrics'' is to improve the care of children with endocrine disorders by promoting basic and clinical knowledge. The journal facilitates the dissemination of information through original papers, mini reviews, clinical guidelines and papers on novel insights from clinical practice. Periodic editorials from outstanding paediatric endocrinologists address the main published novelties by critically reviewing the major strengths and weaknesses of the studies.
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