Systematic mutation analysis of KIAA0767 and KIAA1646 in chromosome 22q-linked periodic catatonia

Background: Periodic catatonia is a familial subtype of schizophrenia characterized by hyperkinetic and akinetic episodes, followed by a catatonic residual syndrome. The phenotype has been evaluated in two independent genome-wide linkage scans with evidence for a major locus on chromosome 15q15, and a second independent locus on chromosome 22q_tel. Methods: In the positional and brain-expressed candidate genes KIAA0767 and KIAA1646, we searched for variants in the complete exons and adjacent splice junctions as well as in parts of the 5′- and 3′-untranslated regions by means of a systematic mutation screening in individuals from chromosome 22q-linked pedigrees. Results: The mutation scan revealed 24 single nucleotide polymorphisms, among them two rare codon variants (KIAA0767: S1591; KIAA1646: V338G). However, both were neither found segregating with the disease in the respective pedigree nor found at a significant frequency in a case-control association sample. Conclusions: Starting from linkage signals at chromosome22q_tel in periodic catatonia, we screened two positional brain-expressed candidate genes for genetic variation. Our study excludes genetic variations in the coding and putative promoter regions of KIAA0767 and KIAA1646 as causative factors for periodic catatonia.