Background: The MLC1, located on chromosome 22q13.33, has been suggested as a risk gene for schizophrenia, especially the periodic catatonia subtype. An initially identified missense mutation was found to be extremely rare in other patient cohorts; however, a recent report again argued for an association of two intronic MLC1 single nucleotide polymorphisms (SNPs) with schizophrenia and bipolar disorder.
Methods: A case-control study of these polymorphisms as well as SNPs in the transcriptional control region of MLC1 was conducted in 212 chronic schizophrenic patients, 56 of which suffered from periodic catatonia, 106 bipolar patients, and 284 controls.
Results: Both intronic and promoter polymorphisms were specifically and significantly associated with periodic catatonia but not schizophrenia or bipolar disorder in general. A haplotype constructed from all polymorphisms was also associated with periodic catatonia.
Conclusions: The MLC1 variation is associated with periodic catatonia; whether it constitutes a susceptibility or a modifier gene has to be determined.