Linkage analysis between manic-depressive illness and the region on chromosome 15q involved in Prader-Willi syndrome, including two GABAA receptor subtype genes.
Cooccurrence of Prader-Willi syndrome and psychosis has been reported in a few cases. Prader-Willi syndrome is most often associated with interstitial deletion or uniparental disomy of chromosome 15q11-q13. The cooccurrence of Prader-Willi syndrome and psychosis may thus be due to deletion of, or in the case of uniparental disomy, duplication of a gene involved in the etiology of psychosis, possibly manic-depressive illness localized in this region. The region contains two assumed candidate genes for manic-depressive illness, the alpha 5 and beta 3 subunits of the gamma-aminobutyric acid (GABA)A receptor. This study investigates linkage between manic-depressive illness and this region. Furthermore, an additional case with Prader-Willi syndrome and psychosis is briefly described. No evidence of linkage was found assuming dominant or recessive modes of inheritance. Linkage to the GABAA receptor subunits was excluded assuming a dominant mode of transmission for all models, and to the proximal part of the chromosome 15q11-q13 region for broader phenotypic models. Negative though largely inconclusive lod scores were obtained assuming a recessive mode of transmission; however close linkage to the beta 3 subtype of the GABAA receptor was excluded.
Ewald
H
H
Department of Psychiatric Demography, Psychiatric Hospital, Aarhus, Denmark.
Mors
O
O
Flint
T
T
Kruse
T A
TA
D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D010375:Pedigree; D011218:Prader-Willi Syndrome / Q000235:genetics*; D018079:Receptors, GABA / Q000235:genetics*
D018079:Receptors, GABA