CACNA1H Mutations Are Associated With Different Forms of Primary Aldosteronism

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• 作者：Georgios Daniil^a ; ^b ; ¹ ; Fabio L Fernandes-Rosa^a ; ^b ; ^c ; ¹ ; ^{fabio.fernandes-rosa@inserm.fr} ; Jean Chemin^d ; ^e ; Iulia Blesneac^d ; ^e ; Jacques Beltrand^b ; ^f ; ^g ; ^h ; Michel Polak^b ; ^f ; ^g ; ^h ; Xavier Jeunemaitre^a ; ^b ; ^c ; Sheerazed Boulkroun^a ; ^b ; Laurence Amar^a ; ^b ; ⁱ ; Tim M Strom^j ; ^k ; Philippe Lory^d ; ^e ; Maria-Christina Zennaro^a ; ^b ; ^c ; ^{maria-christina.zennaro@inserm.fr}
• 关键词：PA ; primary aldosteronism ; APA ; aldosterone producing adenoma ; FH ; familial hyperaldosteronism ; WES ; whole exome sequencing
• 刊名：EBioMedicine
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：13
• 期：Complete
• 页码：225-236
• 全文大小：1558 K
• 卷排序：13

文摘

Germline CACNA1H mutations were identified in patients with different forms of primary aldosteronism (PA) CACNA1H mutations modify electrophysiological channel properties They induce increased aldosterone production and/or expression of genes coding for steroidogenic enzymes Functional modifications are in favor of a gain of function phenotype PA associated to CACNA1H mutations may include early onset PA with multiplex developmental disorder, familial and sporadic forms.Despite recent advances, the pathogenesis of a large proportion of sporadic and familial cases of primary aldosteronism (PA) has not been elucidated. Our work suggests that genetic variants in CACNA1H, coding for the voltage-gated T-type calcium channel Cav3.2, may be responsible for PA with different phenotypic presentations. These mutations affect the electrophysiological channel properties and increase aldosterone production and/or expression of genes coding for steroidogenic enzymes. These findings bring substantial new insight into the genetic and phenotypic spectrum of PA opening new perspectives for genetic screening for CACNA1H mutations in PA, aiming to early diagnosis and better medical care.