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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Rare variants of the gene encoding the potassium chloride co-transporter 3 are associated with bipolar disorder.

Recessive mutations of the potassium chloride co-transporter 3 gene ( SLC12A6 , KCC3 ) cause severe peripheral neuropathy frequently associated with agenesis of the corpus callosum and psychoses (ACCPN). SLC12A6 is localized on chromosome 15q14, a region where linkage to schizophrenia and bipolar disorder has previously been shown. Mutation analysis of SLC12A6 was carried out by direct sequencing of PCR-generated DNA fragments in two affected members of a multiplex family, and three non-affected individuals. A case-control study was performed to assess association of variants with bipolar disorder and schizophrenia in a large sample. Several variants including two rare single nucleotide polymorphisms (G/A, G/A) in the promoter and 5'-UTR, and a thymidine insertion in intron 4 were found. The two G variants and the insertion variant were co-inherited with chromosome 15-related schizophrenia in a large family that strongly supports the region on chromosome 15q14-15 between markers D15S144 and D15S132. Furthermore, they are in linkage disequilibrium with each other, and significantly associated with bipolar disorder in a case-control study. Our data strongly suggest that rare variants of SLC12A6 may represent risk factors for bipolar disorder.[1]


  1. Rare variants of the gene encoding the potassium chloride co-transporter 3 are associated with bipolar disorder. Meyer, J., Johannssen, K., Freitag, C.M., Schraut, K., Teuber, I., Hahner, A., Mainhardt, C., Mössner, R., Volz, H.P., Wienker, T.F., McKeane, D., Stephan, D.A., Rouleau, G., Reif, A., Lesch, K.P. Int. J. Neuropsychopharmacol. (2005) [Pubmed]
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