LINKAGE ANALYSIS BETWEEN MANIC-DEPRESSIVE ILLNESS AND THE REGION ON CHROMOSOME-15Q INVOLVED IN PRADER-WILLI-SYNDROME, INCLUDING 2 GABA(A) 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 in terstitial deletion or uniparental disomy of chromosome 15q11-q13. The cooccurrence of Prader-Willi syndrome and psychosis may thus be due t o 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 cand idate genes for manic-depressive illness, the alpha(5) and beta(3) sub units of the gamma-aminobutyric acid (GABA)(A) receptor. This study in vestigates linkage between manic-depressive illness and this region. F urthermore, an additional case with Prader-Willi syndrome and psychosi s is briefly described. No evidence of linkage was found assuming domi nant 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 f or broader phenotypic models. Negative though largely inconclusive lod scores were obtained assuming a recessive mode of transmission; howev er close linkage to the beta(3) subtype of the GABA(A) receptor was ex cluded.