Biology Reference
In-Depth Information
FIGURE 6.3. Cochlear histopathologic patterns associated with hereditary hearing
impairment in mice (adapted from Steel and Bock 1983). Neuroepithelial defects
are characterized by a Reissner's membrane (RM) that is in normal position, and
an initially normal-appearing stria vascularis (SV). Ionic homeostatic defects (also
known as cochleosaccular degeneration) may include a primary strial abnormality,
which leads to collapse of Reissner's membrane and secondary damage to the organ
of Corti (OC).
The value of having many unrelated families segregating mutations at the
same nonsyndromic or syndromic deafness locus cannot be overstated.
Additional families linked to the same locus are a potential source of infor-
mative meiotic recombinants that may narrow the chromosomal interval
encompassing the disease gene. Among unrelated linked families, multiple
alleles are suggested when there is more than one haplotype in the region
of the disease gene. Multiple independently arising mutant alleles also
provide a stronger argument for a causal connection between the mutated
gene and the hearing-loss phenotype.
3. DFNA, DFNB and DFN Loci
3.1 General Remarks
When “DFN”, the acronym for deafness, is followed directly by a number
(e.g.,
DFN2
), the locus maps to the X-chromosome. When “DFN” is
followed either by “A” or “B,” the mutant allele is an autosomal dominant
