The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
CLCN2 chloride channel mutations in familial hyperaldosteronism type II
Open accessAbstract
Primary aldosteronism, a common cause of severe hypertension1, 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. Whole-exome sequencing identifies mutations in CLCN2 in individuals with familial hyperaldosteronism type II or early-onset primary aldosteronism. These gain-of-function mutations cause chloride channel opening and glomerulosa cell depolarization, showing a role for anion channels in aldosterone production.
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Analysis of protein-coding genetic variation in 60,706 humans
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Differential analysis of gene regulation at transcript resolution with RNA-seq
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Self-citationZhou, B., Bentham, J., Di Cesare, M., Bixby, H., Danaei, G., Cowan, M. J., Paciorek, C. J., Singh, G., Hajifathalian, K., Bennett, J. E., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(16)31919-5 · Cited by 2,579
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K + Channel Mutations in Adrenal Aldosterone-Producing Adenomas and Hereditary Hypertension
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Self-citationA framework for the interpretation of de novo mutation in human disease
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Cited by
CLC Chloride Channels and Transporters: Structure, Function, Physiology, and Disease
Jentsch, T. J., & Pusch, M. (2018) · Physiological Reviews · doi:10.1152/physrev.00047.2017 · Cited by 448
Diagnosis and treatment of primary aldosteronism: practical clinical perspectives
Young, W. F. (2019) · Journal of Internal Medicine · doi:10.1111/joim.12831 · Cited by 325
Mulatero, P., Monticone, S., Deinum, J., Amar, L., Prejbisz, A., Zennaro, M.-C., Beuschlein, F., Rossi, G. P., Nishikawa, T., Morganti, A., et al. (2020) · Journal of Hypertension · doi:10.1097/hjh.0000000000002510 · Cited by 317
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Steroid Metabolome Analysis in Disorders of Adrenal Steroid Biosynthesis and Metabolism
Storbeck, K.-H., Schiffer, L., Baranowski, E. S., Chortis, V., Prete, A., Barnard, L., Gilligan, L. C., Taylor, A. E., Idkowiak, J., Arlt, W., et al. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00262 · Cited by 141
Metadata
- Authors
- 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., McKenney, D., Lash, R. W., Jones, D. P., Chune, G., Gagliardi, P., Choi, M., Gordon, R., Stowasser, M., Fahlke, C., & Lifton, R. P.
- Venue
- Nature Genetics
- Published
- 2018-02-05
- Volume
- 50
- Issue
- 3
- Pages
- 349-354
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2793806343
- Cited by
- 266
- References
- 51
- FWCI
- 21.15
- Type
- journal article
- Language
- en
- Open access
- green
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- 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. https://doi.org/10.1038/s41588-018-0048-5
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