A DUPLICATION PARACENTRIC INVERSION ASSOCIATED WITH FAMILIAL X-LINKEDDEAFNESS (DFN3) SUGGESTS THE PRESENCE OF A REGULATORY ELEMENT MORE THAN 400 KB UPSTREAM OF THE POU3F4 GENE

X-linked deafness with stapes fixation (DFN3) is caused by mutations i n the POU3F4 gene at Xq21.1. By employing pulsed field gel electrophor esis (PFGE) we identified a chromosomal aberration in the DNA of a DFN 3 patient who did not show alterations in the open reading frame (ORF) of POU3F4. Southern blot analysis indicated that a DNA segment of 150 kb, located 170 kb proximal to the POU3F4 gene, was duplicated. Fluor escence in situ hybridization (FISH) analysis, PFGE, and detailed Sout hern analysis revealed that this duplication is part of a more complex rearrangement including a paracentric inversion involving the Xq21.1 region, and presumably the Xq21.3 region. Since at least two DFN3-asso ciated minideletions are situated proximal to the duplicated segment, the inversion most likely disconnects the POU3F4 gene from a regulator y element which is located at a distance of at least 400 kb upstream o f the POU3F4 gene.