title: Screening of chromosomal region 21q22.3 for mutations in genes associated with neuronal Ca2+ signalling in bipolar affective disorder.
abstract: The therapeutic effect of lithium in bipolar affective disorder may be connected with decreasing intracellular Ca(2+) concentrations. Several linkage studies have identified a potential bipolar affective disorder susceptibility locus within chromosomal region 21q22.3. This locus contains two genes expressed in the brain - ADARB1 and TRPM2 - involved in regulating intracellular Ca(2+) concentrations. The aim of this study was an identification of mutations in the coding sequences of ADARB1 and TRPM2 and their association with bipolar affective disorder. For that purpose we screened 60 patients with bipolar affective disorder and a control group of 66 subjects using single strand conformation polymorphism and sequence analysis. For rapid screening we performed restriction fragment length polymorphism analysis. Screening of bipolar affective disorder patients for mutations in TRPM2 led to identification of three novel and four known transitions. Two transitions resulted in the substitutions: R755C and A890V. Screening of the coding sequence of ADARB1 did not reveal any mutations except one already known transition. A comparison of the transition frequency in patients and controls does not support association of the detected mutations with bipolar affective disorder. According to our results, bipolar affective disorder may not be caused by mutations in ADARB1. However, this study does not exclude TRPM2 as a candidate gene since we have screened only about 30 per cent of the entire coding sequence of this large gene.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznan, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kostyrko
authors.forename: Joanna
authors.initials: J
authors.lastname: Hauser
authors.forename: Janusz K
authors.initials: JK
authors.lastname: Rybakowski
authors.forename: Wiesław H
authors.initials: WH
authors.lastname: Trzeciak
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D009154:Mutation / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D016601:RNA-Binding Proteins; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D050053:TRPM Cation Channels / Q000235:genetics
chemical_list: D016601:RNA-Binding Proteins; D050053:TRPM Cation Channels; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; D002118:Calcium