CLCN2 chloride channel mutations in familial hyperaldosteronism type II

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

CLCN2 chloride channel mutations in familial hyperaldosteronism type II. / Scholl, Ute I; Stölting, Gabriel; Schewe, Julia; Thiel, Anne; Tan, Hua; Nelson-Williams, Carol; Vichot, Alfred A; Jin, Sheng Chih; Loring, Erin; Untiet, Verena; Yoo, Taekyeong; Choi, Jungmin; Xu, Shengxin; Wu, Aihua; Kirchner, Marieluise; Mertins, Philipp; Rump, Lars C; Onder, Ali Mirza; Gamble, Cory; McKenney, Daniel; Lash, Robert W; Jones, Deborah P; Chune, Gary; Gagliardi, Priscila; Choi, Murim; Gordon, Richard; Stowasser, Michael; Fahlke, Christoph; Lifton, Richard P.

In: Nature Genetics, Vol. 50, No. 3, 2018, p. 349-354.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Scholl, UI, Stölting, G, Schewe, J, Thiel, A, Tan, H, Nelson-Williams, C, Vichot, AA, Jin, SC, Loring, E, Untiet, V, Yoo, T, Choi, J, Xu, S, Wu, A, Kirchner, M, Mertins, P, Rump, LC, Onder, AM, Gamble, C, McKenney, D, Lash, RW, Jones, DP, Chune, G, Gagliardi, P, Choi, M, Gordon, R, Stowasser, M, Fahlke, C & Lifton, RP 2018, 'CLCN2 chloride channel mutations in familial hyperaldosteronism type II', Nature Genetics, vol. 50, no. 3, pp. 349-354. https://doi.org/10.1038/s41588-018-0048-5

APA

Scholl, U. I., Stölting, G., Schewe, J., Thiel, A., Tan, H., Nelson-Williams, C., Vichot, A. A., Jin, S. C., Loring, E., Untiet, V., Yoo, T., Choi, J., Xu, S., Wu, A., Kirchner, M., Mertins, P., Rump, L. C., Onder, A. M., Gamble, C., ... Lifton, R. P. (2018). CLCN2 chloride channel mutations in familial hyperaldosteronism type II. Nature Genetics, 50(3), 349-354. https://doi.org/10.1038/s41588-018-0048-5

Vancouver

Scholl UI, Stölting G, Schewe J, Thiel A, Tan H, Nelson-Williams C et al. CLCN2 chloride channel mutations in familial hyperaldosteronism type II. Nature Genetics. 2018;50(3):349-354. https://doi.org/10.1038/s41588-018-0048-5

Author

Scholl, Ute I ; Stölting, Gabriel ; Schewe, Julia ; Thiel, Anne ; Tan, Hua ; Nelson-Williams, Carol ; Vichot, Alfred A ; Jin, Sheng Chih ; Loring, Erin ; Untiet, Verena ; Yoo, Taekyeong ; Choi, Jungmin ; Xu, Shengxin ; Wu, Aihua ; Kirchner, Marieluise ; Mertins, Philipp ; Rump, Lars C ; Onder, Ali Mirza ; Gamble, Cory ; McKenney, Daniel ; Lash, Robert W ; Jones, Deborah P ; Chune, Gary ; Gagliardi, Priscila ; Choi, Murim ; Gordon, Richard ; Stowasser, Michael ; Fahlke, Christoph ; Lifton, Richard P. / CLCN2 chloride channel mutations in familial hyperaldosteronism type II. In: Nature Genetics. 2018 ; Vol. 50, No. 3. pp. 349-354.

Bibtex

@article{f9cecfb301994d8c805c4405e7579e12,
title = "CLCN2 chloride channel mutations in familial hyperaldosteronism type II",
abstract = "Primary aldosteronism, a common cause of severe hypertension 1 , features constitutive production of the adrenal steroid aldosterone. We analyzed a multiplex family with familial hyperaldosteronism type II (FH-II) 2 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.",
author = "Scholl, {Ute I} and Gabriel St{\"o}lting and Julia Schewe and Anne Thiel and Hua Tan and Carol Nelson-Williams and Vichot, {Alfred A} and Jin, {Sheng Chih} and Erin Loring and Verena Untiet and Taekyeong Yoo and Jungmin Choi and Shengxin Xu and Aihua Wu and Marieluise Kirchner and Philipp Mertins and Rump, {Lars C} and Onder, {Ali Mirza} and Cory Gamble and Daniel McKenney and Lash, {Robert W} and Jones, {Deborah P} and Gary Chune and Priscila Gagliardi and Murim Choi and Richard Gordon and Michael Stowasser and Christoph Fahlke and Lifton, {Richard P}",
year = "2018",
doi = "10.1038/s41588-018-0048-5",
language = "English",
volume = "50",
pages = "349--354",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "3",

}

RIS

TY - JOUR

T1 - CLCN2 chloride channel mutations in familial hyperaldosteronism type II

AU - Scholl, Ute I

AU - Stölting, Gabriel

AU - Schewe, Julia

AU - Thiel, Anne

AU - Tan, Hua

AU - Nelson-Williams, Carol

AU - Vichot, Alfred A

AU - Jin, Sheng Chih

AU - Loring, Erin

AU - Untiet, Verena

AU - Yoo, Taekyeong

AU - Choi, Jungmin

AU - Xu, Shengxin

AU - Wu, Aihua

AU - Kirchner, Marieluise

AU - Mertins, Philipp

AU - Rump, Lars C

AU - Onder, Ali Mirza

AU - Gamble, Cory

AU - McKenney, Daniel

AU - Lash, Robert W

AU - Jones, Deborah P

AU - Chune, Gary

AU - Gagliardi, Priscila

AU - Choi, Murim

AU - Gordon, Richard

AU - Stowasser, Michael

AU - Fahlke, Christoph

AU - Lifton, Richard P

PY - 2018

Y1 - 2018

N2 - Primary aldosteronism, a common cause of severe hypertension 1 , features constitutive production of the adrenal steroid aldosterone. We analyzed a multiplex family with familial hyperaldosteronism type II (FH-II) 2 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.

AB - Primary aldosteronism, a common cause of severe hypertension 1 , features constitutive production of the adrenal steroid aldosterone. We analyzed a multiplex family with familial hyperaldosteronism type II (FH-II) 2 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.

U2 - 10.1038/s41588-018-0048-5

DO - 10.1038/s41588-018-0048-5

M3 - Journal article

C2 - 29403011

VL - 50

SP - 349

EP - 354

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 3

ER -

ID: 209898480