Both authors contributed equally to this paper.
Mutational spectrum in the Ca2+-activated cation channel gene TRPM4 in patients with cardiac conductance disturbances†
Article first published online: 20 OCT 2011
© 2011 Wiley Periodicals, Inc.
Volume 33, Issue 1, pages 109–117, January 2012
How to Cite
Stallmeyer, B., Zumhagen, S., Denjoy, I., Duthoit, G., Hébert, J.-L., Ferrer, X., Maugenre, S., Schmitz, W., Kirchhefer, U., Schulze-Bahr, E., Guicheney, P. and Schulze-Bahr, E. (2012), Mutational spectrum in the Ca2+-activated cation channel gene TRPM4 in patients with cardiac conductance disturbances. Hum. Mutat., 33: 109–117. doi: 10.1002/humu.21599
Communicated by Nancy B. Spinner
- Issue published online: 14 DEC 2011
- Article first published online: 20 OCT 2011
- Accepted manuscript online: 1 SEP 2011 08:16AM EST
- Manuscript Accepted: 17 AUG 2011
- Manuscript Received: 15 APR 2011
- Deutsche Forschungsgemeinschaft (DFG 653/Ki13-1 and 13-2)
- Fondation Leducq (Paris); IZKF (Münster); GIS Institut des Maladies Rares
- Association Française contre les myopathies (AFM; Paris) (ANR-06-MRAR-022-01)
- cardiac conduction disease;
- right-bundle branch block;
- atrioventricular block
Very recently, mutations in the TRPM4 gene have been identified in four pedigrees as the cause of an autosomal dominant form of cardiac conduction disease. To determine the role of TRPM4 gene variations, the relative frequency of TRPM4 mutations and associated phenotypes was assessed in a cohort of 160 unrelated patients with various types of inherited cardiac arrhythmic syndro-mes. In eight probands with atrioventricular block or right bundle branch block—five familial cases and three spora-dic cases—a total of six novel and two published TRPM4 mutations were identified. In patients with sinus node dysfunction, Brugada syndrome, or long-QT syndrome, no mutations were found. The novel mutations include six amino acid substitutions and appeared randomly distributed through predicted TRPM4 protein. In addition, eight polymorphic sites including two in-frame deletions were found. Mutations separated from polymorphisms by absence in control individuals and familial cosegregation in some families. In summary, TRPM4 gene mutations appear to play a major role in cardiac conduction disease but not for other related syndromes so far. The phenotypes are variable and clearly suggestive of additional factors modulating the disease phenotype in some patients. Hum Mutat 33:109–117, 2012. © 2011 Wiley Periodicals, Inc.