Abstract 808 Poster Session IV, Tuesday, 5/4 (poster 203)

Records of disease-causing mutations are important for diagnosis, prenatal diagnosis and treatment of disease. They are relevant for health care workers including physicians and genetic counselors. Database information also serves in developing predictive information regarding phenotypic outcome. We have developed Hexadb, a locus-specific database recording disease producing and other allelic variants at the human HEXA (Tay-Sachs disease, TSD) gene locus. HEXAdb is a relational database accessed via an SQL engine running on an i686 UNIX platform, hosted on the Internet at http://data.mch.mcgill.ca/hexadb. Ninety-eight mutations are presently recorded along with additional information. Seventy-six mutations are listed as causing a GM2 gangliosidosis with a known clinical phenotype, three as benign, seven as producing neutral polymorphisms. Among twelve alleles for which no associated clinical phenotype has been described, six are predicted to be disease causing. The database contains information about the HEXA gene structure, cDNA sequence, exon/intron boundaries, polymorphic markers and pseudoalleles, The effect of mutation on DNA, RNA, protein, clinical and biochemical phenotype are recorded. Where relevant, geographic or ethnic association of alleles are included. Reference citations are given for all mutations. Information for parents (and/or health care workers) about the medical significance of Tay-Sachs disease, treatment and screening is described in a clinical page. A field is being developed to map HEXA mutations onto the homology-modelled hexosaminidase structure ( Tews et al, Nature Structural Biology, 1996) to provide information regarding the effects of mutations on the manifestations of disease. A field describing the status of TSD screening is also being considered. Such a field would be collaborative and might include information regarding: allele frequencies/numbers of alleles screened annually according to ethnic/geographic origin, number of affected fetuses identified by prenatal testing according to ethnic/geographic origin, screening tests for specific alleles, NTSAD approved screening centres etc. A mutation submission form will be available online shortly. The exponential growth of information regarding allelic variation accounting for cause of and/or susceptibility to disease mandates the creation of a formal record of "mutation" at gene loci. The current pace of mutation discovery far exceeds the capacity to publish the data by conventional means. The HEXA database and others like it will serve the interests of genomics, human genetic diversity, medicine and the needs of patients, families and communities.

funded by the RMGA (Reseau de Medecine Genetique Appliquee) of the FRSQ (Fonds de la Recherche en Sante du Quebec)