Biology Reference
In-Depth Information
FIGURE 6.6. Postulated structure of the Pendred syndrome gene product (modified
from Everett et al. 1997), and its associated mutations (Coyle et al. 1998; Cremers
et al. 1998; Everett et al. 1997; Van Hauwe et al. 1998). The deduced amino acid
sequence has ten predicted transmembrane domains, and is thought to transport
chloride and/or iodide across cell membranes (Everett et al. 1997; Scott et al. 1998).
5.2.3 Pathogenesis of Hearing Loss in Pendred Syndrome
Establishing a direct pathogenetic link between
PDS
mutations and thyroid
dysfunction is relatively simple. The demonstration that pendrin transports
iodine across cell membranes suggests a direct mechanism for the observed
inability to incorporate iodine into thyroid hormone in Pendred's syndrome
(Scott et al. 1998).
The relationship of
PDS
to the development and function of the cochlea
is less obvious. It is possible that the cochlear abnormalities are caused
by thyroid dysfunction during development of the cochlea. Congenitally
hypothyroid (
hyt/hyt
) mice have sensorineural hearing loss associated with
abnormalities of the outer and inner hair cells (O'Malley et al. 1995).
However, the cochleae of
hyt/hyt
mice are not malformed (O'Malley et al.
1995), suggesting that hypothyroidism itself does not necessarily cause
cochlear malformations in mice. Therefore the inner ear malformations
observed in Pendred syndrome might not be directly caused by hypothy-
roidism in utero. An alternative hypothesis is that pendrin plays a more
