title: Mutational spectrum in the Ca(2+)--activated cation channel gene TRPM4 in patients with cardiac conductance disturbances.
abstract: 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 syndromes. In eight probands with atrioventricular block or right bundle branch block--five familial cases and three sporadic 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.
authors: Institut für Genetik von Herzerkrankungen, Universitätsklinikum Münster, Münster, Germany. birgit.stallmeyer@ukmuenster.de
authors: Birgit
authors: B
authors: Stallmeyer
authors: Sven
authors: S
authors: Zumhagen
authors: Isabelle
authors: I
authors: Denjoy
authors: Guillaume
authors: G
authors: Duthoit
authors: Jean-Louis
authors: JL
authors: Hébert
authors: Xavier
authors: X
authors: Ferrer
authors: Svetlana
authors: S
authors: Maugenre
authors: Wilhelm
authors: W
authors: Schmitz
authors: Uwe
authors: U
authors: Kirchhefer
authors: Ellen
authors: E
authors: Schulze-Bahr
authors: Pascale
authors: P
authors: Guicheney
authors: Eric
authors: E
authors: Schulze-Bahr
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D054537:Atrioventricular Block / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D002037:Bundle-Branch Block / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic; D017384:Sequence Deletion; D050053:TRPM Cation Channels / Q000235:genetics*
chemical_list: D050053:TRPM Cation Channels; C437888:TRPM4 protein, human; D002118:Calcium