Is the WKL1 gene associated with schizophrenia?

Area of Science:

• Neurogenetics
• Molecular Psychiatry
• Schizophrenia Research

Background:

• A previous study suggested a WKL1 gene missense mutation (Leu309Met) co-segregated with periodic catatonic schizophrenia (SCZ).
• The WKL1 gene encodes a putative cation channel protein exclusively expressed in the brain.
• This raised questions about the mutation's role in SCZ, its effect on channel function, and WKL1 gene expression levels in SCZ.

Purpose of the Study:

• To investigate the role of the WKL1 gene Leu309Met mutation in schizophrenia susceptibility.
• To determine if the Leu309Met mutation affects WKL1 channel activity.
• To compare WKL1 gene expression levels in the brains of SCZ patients and controls.

Main Methods:

• Screening the Leu309Met mutation in 117 Israeli SCZ patients and 176 controls.
• Analyzing WKL1 gene expression in postmortem dorsalateral prefrontal cortex from 16 SCZ patients and 15 controls.
• Measuring the channel activity of normal and mutated WKL1 in vitro.

Main Results:

• The Leu309Met mutation was not found to be associated with SCZ in the studied Israeli population.
• No significant differences in WKL1 gene expression were observed between SCZ brains and controls.
• In vitro studies did not reveal a significant impact of the Leu309Met mutation on WKL1 channel activity.

Conclusions:

• The findings argue against the involvement of the WKL1 gene and the Leu309Met mutation in schizophrenia susceptibility.
• WKL1 gene expression levels in the dorsalateral prefrontal cortex do not appear to be altered in SCZ.
• The Leu309Met mutation likely does not functionally impair the WKL1 cation channel.