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 22qtel.


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: S159I; 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 chromosome22qtel 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.
Stöber
Gerald
G
Department of Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany. stoeber_g@klinik.uni-wuerzburg.de
Kohlmann
Bernd
B
Iekiera
Markus
M
Rubie
Claudia
C
Gawlik
Micha
M
Möller-Ehrlich
Kerstin
K
Meitinger
Thomas
T
Bettecken
Thomas
T
D016022:Case-Control Studies; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005190:Family; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D024101:Mitochondrial Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012560:Schizophrenia, Catatonic / Q000145:classification / Q000235:genetics*
D003062:Codon; C503369:GRAMD4 protein, human; D024101:Mitochondrial Proteins