Biology Reference
In-Depth Information
Marshall syndrome mutations in these genes may cause sensorineural
hearing loss by a direct effect on the biomechanical properties of extracel-
lular matrices in the cochlea. Alternatively, in addition to their structural
roles as extracellular matrix constituents, these mutations may regulate
cochlear physiology or homeostasis via other mechanisms. Distinct roles for
each of the subunits are indicated by differences in their expression pat-
terns (Lui et al. 1995; Mayne et al. 1993; Tsumaki et al. 1996; Yoshioka et
al. 1995), tissue-specific alternative splicing (Oxford et al. 1995; Yoshioka et
al. 1995; Zhidkova et al. 1995), and their contributions to heterotypic fibril
formation in bone and the vitreous humor of the eye (Mayne et al. 1993;
Niyibizi and Eyre 1989). In addition, the mammalian discoidin domain
receptors (
DDR1
and
DDR2
) with tyrosine kinase domains are activated
upon receptor binding to fibrillar collagens (Shrivastava et al. 1997; Vogel
et al. 1997), suggesting that extracellular collagen could directly modulate
cellular responses such as growth and senescence.
5.2 Pendred Syndrome
5.2.1 Phenotype
Pendred syndrome (OMIM 274600) is an autosomal recessive disorder
characterized by sensorineural hearing loss in association with thyroid
gland enlargement. The thyroid dysfunction is biochemically characterized
by defective organic binding of iodine (Fraser 1960; Sheffield et al. 1996).
Serologic studies of thyroxin and thyrotropin levels may be normal, espe-
cially in patients tested early during the course of the disease (Cremers et
al. 1998). The best method for detecting the thyroid organification defect is
thought to be the perchlorate discharge test (Reardon et al. 1997), which
reveals an abnormally high level of discharge of exogenously administered
radioactive iodine from the thyroid gland in response to administration of
perchlorate (Fraser 1960).
The hearing loss associated with Pendred syndrome is usually congen-
ital and bilateral, and the severity may range from mild to profound
(Kabakkaya et al. 1993). Vestibular function is variable in patients in whom
it has been studied (Fraser 1965; Illum et al. 1972). A high proportion of
affected individuals have radiologically detectable malformations of the
inner ear (Johnsen et al. 1987). Johnsen et al. (1986) histologically studied
six ears from five patients with Pendred syndrome and found bony cochlear
changes consistent with the Mondini malformation in all preparations. The
classic Mondini inner ear deformity includes a reduced number of turns of
the cochlea, in comparison with the normal 2 1/2 turns, absence of the inter-
scalar septum between turns of the cochlea, enlarged vestibules, abnormal
semicircular canals, and enlarged vestibular aqueducts (Schuknecht 1980).
A more recent study utilizing CT and MRI scanning concluded that the
