title: Analysis of Single Nucleotide Polymorphisms (SNPs) of the small-conductance calcium activated potassium channel (SK3) gene as genetic modifier of the cardiac phenotype in myotonic dystrophy type 1 patients.
abstract: Myotonic dystrophy type 1 (DM1) is the most frequently inherited neuromuscular disease in adults. It is a multisystemic disorder with major cardiac involvement most commonly represented by first-degree atrioventricular heart block (AVB), followed by different degrees of bundle-branch and intraventricular blocks In search for candidate genes, modifiers of the AVB phenotype in DM1, the expression of the small-conductance calcium activated potassium channel (SK3) gene was analysed in muscle biopsies from DM1 patients. The association between SK3 polymorphisms and the AVB phenotype was then studied analyzing 40 DM1 patients with AVB and 40 age-matched DM1 affected individuals with no ECG abnormalities. [CTG]n repeat length and cardiac clinical picture were also assessed for correlation. QRT-PCR experiments showed an over-expression of the SK3 transcript in DM1 muscle biopsies compared to healthy controls. However, no statistical association between the AVB phenotype and either the [CTG]n expansion length or the presence of specific SNPs in the SK3 gene were detected. These findings suggest that modifier genes, other than SK3, should be identified in order to explain the cardiac phenotypic variability among DM1 patients.
authors.affiliation: Department of Biopathology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Rinaldi
authors.forename: A
authors.initials: A
authors.lastname: Botta
authors.forename: L
authors.initials: L
authors.lastname: Vallo
authors.forename: G
authors.initials: G
authors.lastname: Contino
authors.forename: A
authors.initials: A
authors.lastname: Morgante
authors.forename: R
authors.initials: R
authors.lastname: Iraci
authors.forename: C
authors.initials: C
authors.lastname: Catalli
authors.forename: G
authors.initials: G
authors.lastname: Silvestri
authors.forename: V M
authors.initials: VM
authors.lastname: Ventriglia
authors.forename: L
authors.initials: L
authors.lastname: Politano
authors.forename: G
authors.initials: G
authors.lastname: Novelli
mesh_terms: D000328:Adult; D054537:Atrioventricular Block / Q000453:epidemiology / Q000235:genetics*; D001706:Biopsy; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D009223:Myotonic Dystrophy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: C406328:KCNN3 protein, human; D012333:RNA, Messenger; D051640:Small-Conductance Calcium-Activated Potassium Channels