Immunological diagnosis of Werner syndrome by down-regulated and truncatedgene products

Although immunological methods are widely used to diagnose various infectio us diseases, they have rarely been employed to detect genetic diseases. In this study, we have established an immunoblot analysis system for the diagn osis of Werner syndrome (WS), a recessive genetic disorder causing prematur e aging and an enhanced risk of rare cancers. The method uses an immunoblot technique with specific monoclonal antibodies to WS gene product, and B-ly mphoblastoid cell lines (LCLs) transformed by Epstein-Barr virus; these cel l lines express an increased level of normal WS gene product DNA helicase. The method clearly distinguishes normal from patient LCLs containing any of the mutation types found so far in Japan, primarily because of the drastic ally reduced levels of mutated gene products, and secondarily because of th e truncated product sizes. A comparison of this immunological diagnosis wit h the symptom-based clinical diagnosis has narrowed down the criteria of sy mptoms essential for WS diagnosis. This procedure is compatible with, and h as some advantage over, the genetic method, because WS patients can be diag nosed without determining the mutated gene sequences. The method exemplifie d in WS may also be applied to detect some other genetic diseases.