Polyglutamine-containing proteins in schizophrenia

Genetic anticipation, manifested by increased severity and earlier age-at-o nset of the disease over successive generations, is reported in schizophren ia, The molecular basis of anticipation in several neurodegenerative diseas es is unstable coding CAG repeat expansions, Anticipation was reported in s chizophrenia, Recently, studies suggested that enlarged CAG/CTG repeats are over represented in schizophrenic patients compared to normal controls. To gether, these observations suggest that unstable CAG repeats may play a rol e in the etiology of schizophrenia, The purpose of this study is to test fo r the presence of polyglutamine-expanded tracts, encoded by CAG repeats, in total protein extracts derived from lymphoblastoid cell lines of schizophr enic patients, Proteins from schizophrenic patients (n = 59) and normal con trols (n = 73) were separated by means of SDS-polyacrylamide gel electropho resis, wet blotted onto nitrocellulose membrane and probed with a monoclona l antibody (mab 1C2) recognizing expanded polyglutamine arrays, Three abnor mal bands corresponding to protein(s) of molecular weight of approximately 50 kDa were identified in two unrelated schizophrenic patients and in a sib ling of one of these patients. None of the normal controls tested positive for this abnormal band, These results suggest that expanded polyglutamine-c ontaining proteins, though rare, may play a role in the pathogenesis of sch izophrenia.