No missense mutation of WKL1 in a subgroup of probands with schizophrenia

J. M. Devaney, E. A. Donarum, K. M. Brown, J. Meyer, G. Stöber, K. P. Lesch, Gerald Nestadt, D. A. Stephan, Ann E Pulver

Research output: Contribution to journalArticle

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 Leu309-Met 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.

Original languageEnglish (US)
Pages (from-to)419-423
Number of pages5
JournalMolecular Psychiatry
Volume7
Issue number4
DOIs
StatePublished - Jan 1 2002

Fingerprint

Missense Mutation
Schizophrenia
Single Nucleotide Polymorphism
Catatonia
Mutation
Caudate Nucleus
3' Untranslated Regions
Pedigree
Amygdala
Thalamus
Genes
Membrane Proteins
Nucleotides
Chromosomes
Alleles
Genome
Phenotype
Amino Acids
Brain

Keywords

  • 22q13.33
  • Catatonia
  • Mutations
  • Schizophrenia
  • WKL1

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Devaney, J. M., Donarum, E. A., Brown, K. M., Meyer, J., Stöber, G., Lesch, K. P., ... Pulver, A. E. (2002). No missense mutation of WKL1 in a subgroup of probands with schizophrenia. Molecular Psychiatry, 7(4), 419-423. https://doi.org/10.1038/sj.mp.4001022

No missense mutation of WKL1 in a subgroup of probands with schizophrenia. / Devaney, J. M.; Donarum, E. A.; Brown, K. M.; Meyer, J.; Stöber, G.; Lesch, K. P.; Nestadt, Gerald; Stephan, D. A.; Pulver, Ann E.

In: Molecular Psychiatry, Vol. 7, No. 4, 01.01.2002, p. 419-423.

Research output: Contribution to journalArticle

Devaney, JM, Donarum, EA, Brown, KM, Meyer, J, Stöber, G, Lesch, KP, Nestadt, G, Stephan, DA & Pulver, AE 2002, 'No missense mutation of WKL1 in a subgroup of probands with schizophrenia', Molecular Psychiatry, vol. 7, no. 4, pp. 419-423. https://doi.org/10.1038/sj.mp.4001022
Devaney JM, Donarum EA, Brown KM, Meyer J, Stöber G, Lesch KP et al. No missense mutation of WKL1 in a subgroup of probands with schizophrenia. Molecular Psychiatry. 2002 Jan 1;7(4):419-423. https://doi.org/10.1038/sj.mp.4001022
Devaney, J. M. ; Donarum, E. A. ; Brown, K. M. ; Meyer, J. ; Stöber, G. ; Lesch, K. P. ; Nestadt, Gerald ; Stephan, D. A. ; Pulver, Ann E. / No missense mutation of WKL1 in a subgroup of probands with schizophrenia. In: Molecular Psychiatry. 2002 ; Vol. 7, No. 4. pp. 419-423.
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