CLOSE LINKAGE OF A GENE FOR X-LINKED DEAFNESS TO 3 MICROSATELLITE REPEATS AT XQ21 IN RADIOLOGICALLY NORMAL AND ABNORMAL FAMILIES

We have used three highly polymorphic microsatellite repeats from Xq21 to type families in whom a gene for X Linked deafness with perilympha tic gusher (DFN3) was segregating. All three markers were tightly link ed to the disease in its radiologically normal and abnormal forms, wit h a maximum lod score of 10.37 with DXS995 and 8.41 with DXS986 at zer o recombination, and 14.03 with DXS1002 at theta = 0.01. In an isolate d case of deafness of this type, DXS995 indicated either the first rec ombination observed between the marker and the disease gene or a new m utation in the proband. Southern blotting using a cosmid fragment from the candidate region has confirmed a de novo mutation by showing a de letion in the proband which is not present in his mother as judged by dosage analysis. We also describe a family with a paracentric inversio n associated with a microdeletion and discuss how deletion mapping usi ng these and other markers in the region has helped to define a candid ate region for the gene.