A gene variant contributing to the cause of catatonic schizophrenia in a large pedigree was discovered by scientists of the Julius-Maximilians-University of Wuerzburg, Germany. The variant was detected when a group of psychiatrists, geneticists, and neuroscientists around Klaus-Peter Lesch and Jobst Meyer at the Department of Psychiatry and Psychotherapy investigated genes on human chromosome 22 to elucidate the genetic background of dominantly inherited catatonic schizophrenia, which is characterized by acute psychotic episodes with hallucinations, delusions, and disturbed body movements. The protein encoded by this gene, which has been designated WKL1, shares some features with ion channels. Ion channel proteins are located in the cell membrane and assist transportation of electric currents along neurons. Mutations in the potassium channel KCNA1, another ion channel which is remotely related to WKL1, cause episodic ataxia, a rare movement disorder lacking psychotic episodes.
In the mutated form of WKL1, a leucine amino acid residue is replaced by a methionine within one of seven transmembrane domains. The WKL1 gene transcript was found exclusively in the brain and not in peripheral tissues such as heart, muscle, or liver. Chromosome 22, where the gene is localized, has come into focus based on results of a previously conducted linkage analysis, which is a commonly used method to narrow down chromosomal disease loci.
The discovery of the WKL1 gene, which will be published in MOLECULAR PSYCHIATRY, may lead to a better understanding of the pathophysiological mechanisms underlying the development and long-term outcome of schizophrenia. Future studies need to clarify whether mutations in the WKL1 gene or similar genes may also cause schizophrenia or related disorders in other families and sporadic cases. The development of causal treatments of these devasting and cost-intensive disorders (about 1% of the population is affected by schizophrenia) may now be a
Contact: Ava Martin