X-LINKED MIXED DEAFNESS (DFN3) - CLONING AND CHARACTERIZATION OF THE CRITICAL REGION ALLOWS THE IDENTIFICATION OF NOVEL MICRODELETIONS

We have found that the microsatellite marker AFM207zg5 (DXS995) maps t o all previously described deletions which are associated with X-linke d mixed deafness (DFN3) with or without choroideremia and mental retar dation. Employing this marker and pHU16 (DXS26) we have identified two partially overlapping yeast artificial chromosome clones which were u sed to construct a complete 850 kb cosmid contig. Cosmids from this co ntig have been tested by Southern blot analysis on DNA from 16 unrelat ed males with X-linked deafness. Two novel microdeletions were detecte d in patients which exhibit the characteristic DFN3 phenotype. Both de letions are completely contained within one of the known DFN3-deletion s, but one of them does not overlap with two previously described dele tions in patients with contiguous gene syndromes consisting of DFN3, c horoideremia, and mental retardation. Assuming that only a single gene is involved, this suggests that the DFN3 gene spans a chromosomal reg ion of at least 400 kb.