title: A missense mutation in a novel gene encoding a putative cation channel is associated with catatonic schizophrenia in a large pedigree.
abstract: Schizophrenia is a common and etiologically heterogeneous disorder. Although inheritance of schizophrenic syndromes is complex with genetic and environmental factors contributing to the clinical phenotype, periodic catatonia, a familial subtype of catatonic schizophrenia, appears to be transmitted in an autosomal dominant manner. We report here that a Leu309Met mutation in WKL1, a positional candidate gene on chromosome 22q13.33 encoding a putative non-selective cation channel expressed exclusively in brain, co-segregates with periodic catatonia in an extended pedigree. Structural analyses revealed that this missense mutation results in conformational changes of the mutant protein. Our results not only underscore the importance of genetic mechanisms in the etiology of schizophrenic syndromes, but also provide a better understanding of the pathogenesis and incapacitating course of catatonic schizophrenia and related disorders.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Würzburg, D-97080 Würzburg, Germany. jobst.meyer@mail.uni-wuerzburg.de
authors.forename: J
authors.initials: J
authors.lastname: Meyer
authors.forename: A
authors.initials: A
authors.lastname: Huberth
authors.forename: G
authors.initials: G
authors.lastname: Ortega
authors.forename: Y V
authors.initials: YV
authors.lastname: Syagailo
authors.forename: S
authors.initials: S
authors.lastname: Jatzke
authors.forename: R
authors.initials: R
authors.lastname: Mössner
authors.forename: T M
authors.initials: TM
authors.lastname: Strom
authors.forename: I
authors.initials: I
authors.lastname: Ulzheimer-Teuber
authors.forename: G
authors.initials: G
authors.lastname: Stöber
authors.forename: A
authors.initials: A
authors.lastname: Schmitt
authors.forename: K P
authors.initials: KP
authors.lastname: Lesch
mesh_terms: D000595:Amino Acid Sequence; D001923:Brain Chemistry / Q000235:genetics; D002892:Chromosomes, Human, Pair 22; D005192:Family Health; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D012560:Schizophrenia, Catatonic / Q000235:genetics*
chemical_list: D007473:Ion Channels; C431249:WKL1 cation channel