NOVEL COL4A5 COL4A6 DELETIONS AND FURTHER CHARACTERIZATION OF THE DIFFUSE LEIOMYOMATOSIS-ALPORT-SYNDROME (DL-AS) LOCUS DEFINE THE DL CRITICAL REGION/

Diffuse leiomyomatosis (DL) with Alport syndrome (AS) has been shown t o be associated with contiguous gene deletions of the COL4A5 and COL4A 6 genes, with the COL4A6 breakpoint of the deletions invariably locate d in the large intron 2 of the gene. We describe four YAC clones cover ing the locus and a refined restriction map of the entire COL4A6 gene. These resources have allowed us to make a precise estimate of the siz e of COL4A6 introns 2 and 3, as well as the size of the gene itself. W e also describe five novel deletions which, in conjunction with previo us reports, allow the definition of a 90-kb critical region in which t o search for a gene or other entity involved in the pathogenesis of DL .