title: Periodic catatonia: confirmation of linkage to chromosome 15 and further evidence for genetic heterogeneity.
abstract: We earlier reported significant evidence for linkage on chromosome 15q15 in periodic catatonia, a sub-phenotype of schizophrenic psychoses. The disorder is characterized by qualitative hyperkinetic and akinetic psychomotor disturbances through acute psychotic episodes and debilitating symptoms in the long term, with psychomotor weakness, grimacing facial movements and apathy. Here, we confirm mapping of a major gene locus on chromosome 15q15 in a second genome scan in a new set of four multiplex families. Non-parametric multipoint linkage analyses identified a broad region with a maximum peak of Z(all) =3.91 ( P=0.006) and Z(lr) =3.04 at D15S1234 ( P=0.001), satisfying conventional criteria for confirmed linkage. Parametric affected-only analyses under an autosomal dominant model gave a maximum HLOD score of 1.65 (D15S1234) with an estimated 47% of families being linked. Analysis of individual families showed that one large family showed linkage, whereas two others could be clearly excluded, confirming genetic heterogeneity. No other locus reached suggestive levels of significance. Haplotype analysis on chromosome 15 in this and previously linked families placed the susceptibility region to a 11-cM interval between marker D15S1042 and D15S659. Periodic catatonia is the first sub-phenotype of schizophrenic psychoses with confirmed linkage despite the existence of considerable genetic heterogeneity.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany. stoeber_g@klinik.uni-wuerzburg.de
authors.forename: Gerald
authors.initials: G
authors.lastname: Stöber
authors.forename: Dominik
authors.initials: D
authors.lastname: Seelow
authors.forename: Franz
authors.initials: F
authors.lastname: Rüschendorf
authors.forename: Arif
authors.initials: A
authors.lastname: Ekici
authors.forename: Helmut
authors.initials: H
authors.lastname: Beckmann
authors.forename: André
authors.initials: A
authors.lastname: Reis
mesh_terms: D002389:Catatonia / Q000235:genetics*; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008297:Male; D010375:Pedigree