This novel functional difference between the two fibrillin isoforms enabled us both to map fibrillin-1 HS binding to two sites on opposite sides of TB5 and to explore HS binding by TB5 mutations causing WMS, AD and GD (non-cysteine in WT) mutants, using a site-directed mutagenesis approach. The gene discussed is FBN1; the disease is Weill-Marchesani syndrome.