Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension. / Beuschlein, Felix; Boulkroun, Sheerazed; Osswald, Andrea et al.

I: Nature Genetics, Bind 45, Nr. 4, 17.02.2013, s. 440–444.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Beuschlein, F, Boulkroun, S, Osswald, A, Wieland, T, Nielsen, HN, Lichtenauer, UD, Penton, D, Schack, VR, Amar, L, Fischer, E, Walther, A, Tauber, P, Schwarzmayr, T, Diener, S, Graf, E, Allolio, B, Samson-Couterie, B, Benecke, A, Quinkler, M, Fallo, F, Plouin, P-F, Mantero, F, Meitinger, T, Mulatero, P, Jeunemaitre, X, Warth, R, Vilsen, B, Zennaro, M-C, Strom, TM & Reincke, M 2013, 'Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension', Nature Genetics, bind 45, nr. 4, s. 440–444. https://doi.org/10.1038/ng.2550

APA

Beuschlein, F., Boulkroun, S., Osswald, A., Wieland, T., Nielsen, H. N., Lichtenauer, U. D., Penton, D., Schack, V. R., Amar, L., Fischer, E., Walther, A., Tauber, P., Schwarzmayr, T., Diener, S., Graf, E., Allolio, B., Samson-Couterie, B., Benecke, A., Quinkler, M., ... Reincke, M. (2013). Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension. Nature Genetics, 45(4), 440–444. https://doi.org/10.1038/ng.2550

CBE

Beuschlein F, Boulkroun S, Osswald A, Wieland T, Nielsen HN, Lichtenauer UD, Penton D, Schack VR, Amar L, Fischer E, et al. 2013. Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension. Nature Genetics. 45(4):440–444. https://doi.org/10.1038/ng.2550

MLA

Vancouver

Beuschlein F, Boulkroun S, Osswald A, Wieland T, Nielsen HN, Lichtenauer UD et al. Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension. Nature Genetics. 2013 feb. 17;45(4):440–444. https://doi.org/10.1038/ng.2550

Author

Beuschlein, Felix ; Boulkroun, Sheerazed ; Osswald, Andrea et al. / Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension. I: Nature Genetics. 2013 ; Bind 45, Nr. 4. s. 440–444.

Bibtex

@article{9030ed08fb254cb087c8359396802104,
title = "Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension",
abstract = "Primary aldosteronism is the most prevalent form of secondary hypertension. To explore molecular mechanisms of autonomous aldosterone secretion, we performed exome sequencing of aldosterone-producing adenomas (APAs). We identified somatic hotspot mutations in the ATP1A1 (encoding an Na(+)/K(+) ATPase α subunit) and ATP2B3 (encoding a Ca(2+) ATPase) genes in three and two of the nine APAs, respectively. These ATPases are expressed in adrenal cells and control sodium, potassium and calcium ion homeostasis. Functional in vitro studies of ATP1A1 mutants showed loss of pump activity and strongly reduced affinity for potassium. Electrophysiological ex vivo studies on primary adrenal adenoma cells provided further evidence for inappropriate depolarization of cells with ATPase alterations. In a collection of 308 APAs, we found 16 (5.2%) somatic mutations in ATP1A1 and 5 (1.6%) in ATP2B3. Mutation-positive cases showed male dominance, increased plasma aldosterone concentrations and lower potassium concentrations compared with mutation-negative cases. In summary, dominant somatic alterations in two members of the ATPase gene family result in autonomous aldosterone secretion.",
keywords = "Conn's syndrom, Na,K-ATPase",
author = "Felix Beuschlein and Sheerazed Boulkroun and Andrea Osswald and Thomas Wieland and Nielsen, {Hang N} and Lichtenauer, {Urs D} and David Penton and Schack, {Vivien R} and Laurence Amar and Evelyn Fischer and Anett Walther and Philipp Tauber and Thomas Schwarzmayr and Susanne Diener and Elisabeth Graf and Bruno Allolio and Benoit Samson-Couterie and Arndt Benecke and Marcus Quinkler and Francesco Fallo and Pierre-Francois Plouin and Franco Mantero and Thomas Meitinger and Paolo Mulatero and Xavier Jeunemaitre and Richard Warth and Bente Vilsen and Maria-Christina Zennaro and Strom, {Tim M} and Martin Reincke",
note = "impact factor 35 (ISI web of Knowledge)",
year = "2013",
month = feb,
day = "17",
doi = "10.1038/ng.2550",
language = "English",
volume = "45",
pages = "440–444",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "4",

}

RIS

TY - JOUR

T1 - Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension

AU - Beuschlein, Felix

AU - Boulkroun, Sheerazed

AU - Osswald, Andrea

AU - Wieland, Thomas

AU - Nielsen, Hang N

AU - Lichtenauer, Urs D

AU - Penton, David

AU - Schack, Vivien R

AU - Amar, Laurence

AU - Fischer, Evelyn

AU - Walther, Anett

AU - Tauber, Philipp

AU - Schwarzmayr, Thomas

AU - Diener, Susanne

AU - Graf, Elisabeth

AU - Allolio, Bruno

AU - Samson-Couterie, Benoit

AU - Benecke, Arndt

AU - Quinkler, Marcus

AU - Fallo, Francesco

AU - Plouin, Pierre-Francois

AU - Mantero, Franco

AU - Meitinger, Thomas

AU - Mulatero, Paolo

AU - Jeunemaitre, Xavier

AU - Warth, Richard

AU - Vilsen, Bente

AU - Zennaro, Maria-Christina

AU - Strom, Tim M

AU - Reincke, Martin

N1 - impact factor 35 (ISI web of Knowledge)

PY - 2013/2/17

Y1 - 2013/2/17

N2 - Primary aldosteronism is the most prevalent form of secondary hypertension. To explore molecular mechanisms of autonomous aldosterone secretion, we performed exome sequencing of aldosterone-producing adenomas (APAs). We identified somatic hotspot mutations in the ATP1A1 (encoding an Na(+)/K(+) ATPase α subunit) and ATP2B3 (encoding a Ca(2+) ATPase) genes in three and two of the nine APAs, respectively. These ATPases are expressed in adrenal cells and control sodium, potassium and calcium ion homeostasis. Functional in vitro studies of ATP1A1 mutants showed loss of pump activity and strongly reduced affinity for potassium. Electrophysiological ex vivo studies on primary adrenal adenoma cells provided further evidence for inappropriate depolarization of cells with ATPase alterations. In a collection of 308 APAs, we found 16 (5.2%) somatic mutations in ATP1A1 and 5 (1.6%) in ATP2B3. Mutation-positive cases showed male dominance, increased plasma aldosterone concentrations and lower potassium concentrations compared with mutation-negative cases. In summary, dominant somatic alterations in two members of the ATPase gene family result in autonomous aldosterone secretion.

AB - Primary aldosteronism is the most prevalent form of secondary hypertension. To explore molecular mechanisms of autonomous aldosterone secretion, we performed exome sequencing of aldosterone-producing adenomas (APAs). We identified somatic hotspot mutations in the ATP1A1 (encoding an Na(+)/K(+) ATPase α subunit) and ATP2B3 (encoding a Ca(2+) ATPase) genes in three and two of the nine APAs, respectively. These ATPases are expressed in adrenal cells and control sodium, potassium and calcium ion homeostasis. Functional in vitro studies of ATP1A1 mutants showed loss of pump activity and strongly reduced affinity for potassium. Electrophysiological ex vivo studies on primary adrenal adenoma cells provided further evidence for inappropriate depolarization of cells with ATPase alterations. In a collection of 308 APAs, we found 16 (5.2%) somatic mutations in ATP1A1 and 5 (1.6%) in ATP2B3. Mutation-positive cases showed male dominance, increased plasma aldosterone concentrations and lower potassium concentrations compared with mutation-negative cases. In summary, dominant somatic alterations in two members of the ATPase gene family result in autonomous aldosterone secretion.

KW - Conn's syndrom

KW - Na,K-ATPase

U2 - 10.1038/ng.2550

DO - 10.1038/ng.2550

M3 - Journal article

C2 - 23416519

VL - 45

SP - 440

EP - 444

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 4

ER -