Panel Discussion II: Linkage Studies in Tuberous Sclerosis

Abstract

Panel Discussion II: Linkage Studies in Tuberous Sclerosis Current Status and Future Prospects PANEL REPORTER. RAYMOND S. KANDT Division of Neurology in Pediatrics and Medicine Duke University Medical Center Durham, North Carolina 27710 PANEL CHAIR: P. MICHAEL CONNEALLY PANEL MEMBERS: J. MICHAEL CONNOR, JONATHAN L. HAINES, MARGARET PERICAK-VANCE, AND MOYRA SMITH Beginning in 1987 with the report of linkage of tuberous sclerosis (TSC) to the ABO blood group locus on chromosome 9, several research groups attempted to define a precise location for one or more TSC genes. At this conference, further studies on genetic linkage in TSC were reported. The panel discussion, which also included comments from the audience, fo- cused on several issues: the current status of TSC linkage research, banking of cell lines and tissues, clinical and cytogenetic investigations of TSC families and individuals, and possible pathogenetic mechanisms in TSC. CURRENT STATUS Thus far, research in TSC demonstrates at least two genetic phenotypes, one of which is linked to chromosome 9q34 and a second that is probably linked to markers on chromosome 1 Iq. Research also suggests a third phenotype, possibly on chromosome 14. Prior to this meeting, various investigators collaborated in building a TSC linkage dataset. Analyses of the pooled TSC linkage data by different investigators consistently demonstrate genetic heterogeneity in TSC. CELL AND TISSUE BANKING To facilitate localization of t h t causative TSC genes, cell banking can be used. Already, cells from several TSC families are stored in the NIH Human Genetic Mutant Cell Repository in Camden, New Jersey. It was noted that the Camden Repository is not accepting further TSC cell lines. In some cases, the costs of retrieving the cell lines from the Repository may hinder their use. Although bank- ing by individual investigators is also expensive, potential mixups in cell lines can be avoided by using DNA fingerprinting to identify the cell lines. A similar discus- sion was held concerning a TSC tissue bank. Researchers may find it useful to have frozen samples from biopsied lesions or cell lines derived from tissues; however, it was not resolved where and how such tissues would be obtained and stored, or how access to the tissues would occur. Despite concerns about storage,