Journal Article

FZJ-2015-02840

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Recurrent gain of function mutation in calcium channel CACNA1H causes early-onset hypertension with primary aldosteronism

Scholl, U. I. ; Stölting, G.FZJ* ; Nelson-Williams, C. ; Vichot, A. A. ; Choi, M. ; Loring, E. ; Prasad, M. L. ; Goh, G. ; Carling, T. ; Juhlin, C. C. ; Quack, I. ; Rump, L. C. ; Thiel, A. ; Lande, M. ; Frazier, B. G. ; Rasoulpour, M. ; Bowlin, D. L. ; Sethna, C. B. ; Trachtman, H. ; Fahlke, C.FZJ* ; Lifton, R. P. (Corresponding Author)

2015
eLife Sciences Publications Cambridge

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Please use a persistent id in citations: http://hdl.handle.net/2128/8544  doi:10.7554/eLife.06315

Abstract: Many Mendelian traits are likely unrecognized owing to absence of traditional segregation patterns in families due to causation by de novo mutations, incomplete penetrance, and/or variable expressivity. Genome-level sequencing can overcome these complications. Extreme childhood phenotypes are promising candidates for new Mendelian traits. One example is early onset hypertension, a rare form of a global cause of morbidity and mortality. We performed exome sequencing of 40 unrelated subjects with hypertension due to primary aldosteronism by age 10. Five subjects (12.5%) shared the identical, previously unidentified, heterozygous CACNA1HM1549V mutation. Two mutations were demonstrated to be de novo events, and all mutations occurred independently. CACNA1H encodes a voltage-gated calcium channel (CaV3.2) expressed in adrenal glomerulosa. CACNA1HM1549V showed drastically impaired channel inactivation and activation at more hyperpolarized potentials, producing increased intracellular Ca2+, the signal for aldosterone production. This mutation explains disease pathogenesis and provides new insight into mechanisms mediating aldosterone production and hypertension

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Contributing Institute(s):

1. Zelluläre Biophysik (ICS-4)

Research Program(s):

1. 551 - Functional Macromolecules and Complexes (POF3-551) (POF3-551)

Appears in the scientific report 2015

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Database coverage:
; ; ; ; BIOSIS Previews ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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