title: No missense mutation of WKL1 in a subgroup of probands with schizophrenia.
abstract: Recently, a Leu309Met mutation in WKL1 (MLC1, KIAA0027), a gene mapped to chromosome 22q13.33, was reported to co-segregate with periodic catatonia, a clinical sub-type of schizophrenia, in seven members of an extended pedigree.(1) WKL1 encodes a putative membrane protein expressed exclusively in the brain, particularly in the amygdala, nucleus caudatus, thalamus, and hippocampus.(1) We screened WKL1 for etiologic mutations in 28 probands from the United States who were given a consensus diagnosis of schizophrenia and met at least one of these criteria: (1) were from multiplex schizophrenia families where at least two schizophrenic subjects were reported to display catatonic behavior at sometime during the course of their illness; or (2) were from multiplex schizophrenia families where, in a genome scan for schizophrenia susceptibility loci, evidence for excess allele sharing among affected family members for markers in the 22q13 region was seen. In addition, 15 affected subjects from 15 German pedigrees were similarly screened for causative mutations. This German cohort exhibited the catatonia phenotype but had ambiguous linkage to 22q13 and included the mutation-positive proband as a positive control. The 43 probands were screened for base changes in WKL1: 15 SNPs in the non-coding regions of the gene, three SNPs in the 3'UTR, four synonymous coding SNPs and two non-synonymous (amino acid changing) SNPs were identified. We were able to rapidly confirm the Leu309Met nucleotide change in the positive control. No missense mutations were detected in any of the other 42 probands studied. These data exclude the role of WKL1 in schizophrenia susceptibility in the subjects studied.
authors: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
authors: J M
authors: JM
authors: Devaney
authors: E A
authors: EA
authors: Donarum
authors: K M
authors: KM
authors: Brown
authors: J
authors: J
authors: Meyer
authors: G
authors: G
authors: Stöber
authors: K P
authors: KP
authors: Lesch
authors: G
authors: G
authors: Nestadt
authors: D A
authors: DA
authors: Stephan
authors: A E
authors: AE
authors: Pulver
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D012560:Schizophrenia, Catatonic / Q000235:genetics*; D014481:United States
chemical_list: D007473:Ion Channels; C431249:WKL1 cation channel