Iliadou et al. (2006) examined 46 members of a large multigenerational Greek pedigree segregating autosomal dominant nonsyndromic, progressive hearing loss. The 24 affected individuals developed conductive hearing loss at about 10 years of age that soon became mixed; ... Iliadou et al. (2006) examined 46 members of a large multigenerational Greek pedigree segregating autosomal dominant nonsyndromic, progressive hearing loss. The 24 affected individuals developed conductive hearing loss at about 10 years of age that soon became mixed; in some family members, progression of the sensorineural component resulted in a pure sensorineural hearing loss that masked the conductive component. Audiologic analysis revealed an age-independent, frequency-specific conductive component and a progressive, frequency-specific sensorineural component. The presence of an air-bone gap, closing at a frequency of 2,000 Hz, in individuals with conductive or mixed hearing loss, together with the absence of a stapedial reflex in all persons with hearing loss, clinically confirmed the diagnosis of otosclerosis. Pauw et al. (2007) performed a phenotype analysis of 25 members of a Dutch family previously studied by Thys et al. (2007) and found to have suggestive linkage to the OTSC7 locus. The mean reported age of onset of hearing loss was 29 years, and analysis of audiometric data demonstrated a considerable degree of phenotypic variability with no significant progression, although longitudinal follow-up in 1 family member showed age-dependent progression of air and bone conduction and air-bone gap levels. High-resolution CT scan revealed an otospongiotic focus in all affected individuals; CT scan in 5 clinically unaffected family members carrying the disease haplotype showed no otospongiotic focus, implying a penetrance of approximately 55%. However, the authors noted that all 5 clinically unaffected individuals showing linkage to OTSC7 were less than 50 years of age and might yet develop the disease. Pauw et al. (2007) commented that the Dutch family's phenotype was not entirely consistent with that of the earlier reported Greek family, despite the overlap in linkage.
In a large Greek pedigree with otosclerosis mapping to 6q13, Thys et al. (2007) sequenced all 66 exons and the intron-exon boundaries of the candidate gene COL12A1 (120320), known to be expressed in the cochlea, but did not ... In a large Greek pedigree with otosclerosis mapping to 6q13, Thys et al. (2007) sequenced all 66 exons and the intron-exon boundaries of the candidate gene COL12A1 (120320), known to be expressed in the cochlea, but did not find any mutations.