Biology Reference
In-Depth Information
Autosomal and X-Linked
Auditory Disorders
ANDREW J. G RIFFITH and THOMAS B. FRIEDMAN
1. Introduction
Mutations in any one of more than two hundred different genes can cause
hearing loss (Fig. 6.1). This remarkable genetic heterogeneity is a reflection
of the great diversity of highly specialized proteins and cell types required
for the electromechanical transduction of sound stimuli within the auditory
system (Rubsamen and Lippe 1998). This chapter describes our rapidly
evolving knowledge of the genes responsible for syndromic and nonsyn-
dromic deafness. Two treatises of enduring merit predate the recent iden-
tification of many of the genes for syndromic forms of deafness, but their
detailed clinical and classical genetic descriptions remain of great value
(Gorlin et al. 1995; Konigsmark and Gorlin 1976).
The incidence of significant hearing loss among newborns is approxi-
mately 1/1,000 and about 50% of these cases appear to have a genetic eti-
ology (Liu et al. 1994; Marazita et al. 1993; Morton 1991). The proportion
of persons with late-onset hearing loss with a genetic origin is not known.
Many families have been described in which parents transmit defective
genes to their offspring, resulting in hearing loss at birth or later in life
(Fraser 1976; Konigsmark 1969; Nance and Sweeney 1975; Reardon et al.
1992). Dominant and recessive modes of inheritance were noted. The
majority of nonsyndromic sensorineural hearing loss is recessive, 20% is
dominant, and 1 to 3% is X-linked (Marazita et al. 1993). In each of a large
number of multiplex families, the pattern of inheritance of hearing loss
implicates a single major Mendelian trait, either sex-linked, autosomal
dominant or autosomal recessive. Non-Mendelian inheritance of deafness
due to mitochondrial mutations has also been reported and is the subject
of Chapter 7.
Hearing loss can be caused by environmental insults such as perinatal
trauma, prolonged loud noise exposure and barotrauma, injuries to the
skull, radiation, as well as intrauterine or postnatal exposure to ototoxic
drugs or infectious agents (Garetz and Schacht 1996; Nadol 1993; Prasher
1998). Susceptibility to some of these insults has an underlying genetic
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