NEW NONSYNDROMIC X-LINKED SENSORINEURAL HEARING IMPAIRMENT LINKED TO XP21.2

X-linked deafness is a rare cause of hereditary hearing impairment. We have identified a family with X-linked dominant sensorineural hearing impairment, characterized by incomplete penetrance and variable expre ssivity in carrier females, that is linked to the Xp21.2, which contai ns the Duchenne muscular dystrophy (DMD) locus. The auditory impairmen t in affected males was congenital, bilateral, profound, sensorineural , affecting all frequencies, and without evidence of radiographic abno rmality of the temporal bone. Adult carrier females manifested bilater al, mild-to-moderate high-frequency sensorineural hearing impairment o f delayed onset during adulthood. Eighteen commercially available poly morphic markers from the X chromosome, generating a 10-15-cM map, were initially used for identification of a candidate region. DXS997, loca ted within the DMD gene, generated a two-point LOD score of 2.91 at th eta = 0, with every carrier mother heterozygous at this locus. Recombi nation events at DXS332 (located within the DMD locus, 3' to exon 50 o f the dystrophin gene) and at DXS1068 (5' to the brain promoter of the dystrophin gene) were observed. No recombination events were noted wi th the following markers within the DMD locus: 5'DYS II, intron 44, DX S997, and intron 50. There was no clinical evidence of Duchenne or Bec ker muscular dystrophy in any family member. It is likely that this fa mily represents a new locus on the X chromosome, which when mutated re sults in nonsyndromic sensorineural hearing loss and is distinct from the heterogeneous group of X-linked hearing losses that have been prev iously described.