DELINEATION OF 7Q11.2 DELETIONS ASSOCIATED WITH WILLIAMS-BEUREN SYNDROME AND MAPPING OF A REPETITIVE SEQUENCE TO WITHIN AND TO EITHER SIDE OF THE COMMON DELETION

The majority of Williams-Beuren syndrome (WBS) patients have been show n to have a microdeletion within 7q11.2 including the elastin gene loc us. The extent of these deletions has, however, not been well characte rized. Thirty-five deletion patients were tested for all polymorphic m arkers in the 7q11.2 region bounding ELN to define the extent of delet ions associated with WBS. With only one exception, ELN, D7S1870, and o ne copy of the D7S489 locus (D7S489U) were always included in the dele tions. One patient showed lack of maternal inheritance at D7S1870 and not at ELN or D7S489U, A product corresponding to D7S489U was amplifie d from YAC 743G6 and from the P1 clone RMC07P008, thereby localizing b oth to within the common deletion. The boundary of the deleted region on the proximal (centromeric) side is D7S653 and on the distal side is D7S675, neither of which were ever included in the deletion. One locu s, D7S489L, was variably deleted in patients, indicating a minimum of two common breakpoints on the proximal side. At least one additional r epeat amplified by D7S489 (D7S489M) was localized to a YAC contig mapp ing distal to the common deletion. The D7S489 sequence is highly homol ogous to several cDNA clones in the GenBank database and contains an A lu sequence. It is possible that this and/or other repetitive sequence s in this region could play a role in the mechanism of deletion. (C) 1 996 Academic Press, Inc.