title: High frequency of co-segregating CLCN1 mutations among myotonic dystrophy type 2 patients from Finland and Germany.
abstract: Based on previous reports the frequency of co-segregating recessive chloride channel (CLCN1) mutations in families with myotonic dystrophy type 2 (DM2) was suspected to be increased. We have studied the frequency of CLCN1 mutations in two separate patient and control cohorts from Germany and Finland, and for comparison in a German myotonic dystrophy type 1 (DM1) patient cohort. The frequency of heterozygous recessive chloride channel (CLCN1) mutations is disproportionally higher (5 %) in currently diagnosed DM2 patients compared to 1.6 % in the control population (p = 0.037), while the frequency in DM1 patients was the same as in the controls. Because the two genes segregate independently, the prevalence of CLCN1 mutations in the total DM2 patient population is, by definition, the same as in the control population. Our findings are, however, not based on the total DM2 population but on the currently diagnosed DM2 patients and indicate a selection bias in molecular diagnostic referrals. DM2 patients with co-segregating CLCN1 mutation have an increased likelihood to be referred for molecular diagnostic testing compared to DM2 patients without co-segregating CLCN1 mutation.
authors.affiliation: University of Tampere, Neurogenetics, 33520 Tampere, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Suominen
authors.forename: B
authors.initials: B
authors.lastname: Schoser
authors.forename: O
authors.initials: O
authors.lastname: Raheem
authors.forename: S
authors.initials: S
authors.lastname: Auvinen
authors.forename: M
authors.initials: M
authors.lastname: Walter
authors.forename: R
authors.initials: R
authors.lastname: Krahe
authors.forename: H
authors.initials: H
authors.lastname: Lochmüller
authors.forename: W
authors.initials: W
authors.lastname: Kress
authors.forename: B
authors.initials: B
authors.lastname: Udd
mesh_terms: D000328:Adult; D000368:Aged; D018118:Chloride Channels / Q000235:genetics*; D005260:Female; D005387:Finland; D005787:Gene Frequency; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009223:Myotonic Dystrophy / Q000235:genetics*; D010641:Phenotype
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels