@article {444,
	title = {CLCN2 chloride channel mutations in familial hyperaldosteronism type II.},
	journal = {Nat Genet},
	volume = {50},
	year = {2018},
	month = {2018 Mar},
	pages = {349-354},
	abstract = {<p>Primary aldosteronism, a common cause of severe hypertension  , features constitutive production of the adrenal steroid aldosterone. We analyzed a multiplex family with familial hyperaldosteronism type II (FH-II)  and 80 additional probands with unsolved early-onset primary aldosteronism. Eight probands had novel heterozygous variants in CLCN2, including two de novo mutations and four independent occurrences of a mutation encoding an identical p.Arg172Gln substitution; all relatives with early-onset primary aldosteronism carried the CLCN2 variant found in the proband. CLCN2 encodes a voltage-gated chloride channel expressed in adrenal glomerulosa that opens at hyperpolarized membrane potentials. Channel opening depolarizes glomerulosa cells and induces expression of aldosterone synthase, the rate-limiting enzyme for aldosterone biosynthesis. Mutant channels show gain of function, with higher open probabilities at the glomerulosa resting potential. These findings for the first time demonstrate a role of anion channels in glomerulosa membrane potential determination, aldosterone production and hypertension. They establish the cause of a substantial fraction of early-onset primary aldosteronism.</p>},
	issn = {1546-1718},
	doi = {10.1038/s41588-018-0048-5},
	author = {Scholl, Ute I and St{\"o}lting, Gabriel and Schewe, Julia and Thiel, Anne and Tan, Hua and Nelson-Williams, Carol and Vichot, Alfred A and Jin, Sheng Chih and Loring, Erin and Untiet, Verena and Yoo, Taekyeong and Choi, Jungmin and Xu, Shengxin and Wu, Aihua and Kirchner, Marieluise and Mertins, Philipp and Rump, Lars C and Onder, Ali Mirza and Gamble, Cory and McKenney, Daniel and Lash, Robert W and Jones, Deborah P and Chune, Gary and Gagliardi, Priscila and Choi, Murim and Gordon, Richard and Stowasser, Michael and Fahlke, Christoph and Lifton, Richard P}
}
