Detection of polyglutamine expansion in a new acidic protein: a candidate for childhood onset schizophrenia?

Polyglutamine expansion (PGE) encoded by a CAG repeat underlies eight inher ited neurodegenerative diseases, among which is Huntington's disease. CAG e xpansion has also been reported in schizophrenia, suggesting a role for PGE . To investigate the potential role of PGE as a candidate for schizophrenia , we searched for PGE in nuclear families comprising a patient affected by childhood onset schizophrenia (COS, a rare and severe form of the disease) as a variation of the candidate gene approach for identifying susceptibilit y genes. We tested lymphoblastoid cell lines from COS patients (n = 32) by Western blot analysis with 1C2, a monoclonal antibody that specifically rec ognizes long polyglutamines. Eight of 11 unrelated black American COS patie nts showed a 60-kDa (approximately) band indicative of PGE. A strong 60-kDa band (suggestive of a large PGE) was detected in two of the eight positive patients. A weaker 60-kDa band (suggestive of a smaller and non pathogenic PGE) was detected in some unaffected parents or sibs of these two COS pati ents, and in six other black American COS patients. The strong and weak PGE signals were found to correspond to two different proteins. Unrelated blac k Americans unaffected by COS (n = 38) were negative for the strong 60-kDa PGE signal. Healthy white Americans (n = 53) were negative for both the str ong and weak 60-kDa PGE signals. Two-dimensional gel analysis suggested tha t the strong PGE signal corresponds to an acidic (pl 4 approximately) prote in and resulted in a more precise estimation (52-57 kDa) of its relative ma ss. This protein appeared to be not represented in Genbank, as suggested by the exclusion of several candidate CAG repeats. Our data suggest that this acidic protein might be a candidate for COS.