LDLR DATABASE (2ND EDITION) - NEW ADDITIONS TO THE DATABASE AND THE SOFTWARE, AND RESULTS OF THE FIRST MOLECULAR ANALYSIS

Mutations in the LDL receptor gene (LDLR) cause familial hypercholeste rolemia (FH), a common autosomal dominant disorder, The LDLR database is a computerized tool that has been developed to provide tools to ana lyse the numerous mutations that have been identified in the LDLR gene , The second version of the LDLR database contains 140 new entries and the software has been modified to accommodate four new routines, The analysis of the updated data (350 mutations) gives the following infor mations: (i) 63% of the mutations are missense, and only 20% occur in CPG dinucleotides; (ii) although the mutations are widely distributed throughout the gene, there is an excess of mutations in exons 4 and 9, and a deficit in exons 13 and 15; (iii) the analysis of the distribut ion of mutations located within the ligand-binding domain shows that 7 4% of the mutations in this domain affect a conserved amino-acid, and that they are mostly confined in the C-terminal region of the repeats, Conversely, the same analysis in the EGF-like domain shows that 64% o f the mutations in this domain affect a non-conserved amino-acid, and, that they are mostly confined in the N-terminal half of the repeats, The database is now accessible on the World Wide Web at http://www.umd .necker.fr.