Biology Reference
In-Depth Information
direct role in cochlear development. A direct role for pendrin in cochlear
physiology and homeostasis is suggested by highly specific and discrete
patterns of expression of its mRNA in the endolymphatic system, external
sulcus of the cochlea, as well as the utricule and saccule (Everett et al. 1999).
5.2.4
PDS
Mutations Cause Nonsyndromic Hearing Loss (
DFNB4
)
Several recent reports of
PDS
mutations in human subjects with nonsyn-
dromic hearing impairment provide preliminary evidence that the observed
auditory abnormalities are not a secondary effect of thyroid dysfunction.
Li et al. (1998) demonstrated co-segregation of a missense mutation in
PDS
with profound, prelingual, nonsyndromic sensorineural hearing loss associ-
ated with isolated enlargement of the vestibular aqueducts in a large Indian
pedigree. Usami et al. (1998) also has presented evidence that
PDS
muta-
tions may cause nonsyndromic sensorineural hearing loss associated with
enlarged vestibular aqueducts.
The
PDS
gene and its associated mutations illustrate several important
principles of auditory genetics: First, both syndromic and nonsyndromic
deafness may be caused by mutations in the same gene. It is therefore
important to consider syndromic hearing loss genes as candidates for
nonsyndromic hearing impairment, and vice versa (Fig. 6.1). Second, it
is essential to thoroughly ascertain hearing loss families for syndromic man-
ifestations, such as goiter. Reascertainment of the family originally used to
map
DFNB4
revealed the presence of goiters in affected individuals, thus
establishing the diagnosis of Pendred syndrome (B. Bonne-Tamir, personal
communication).
5.3 Waardenburg Syndrome
5.3.1 Phenotype
5.3.1.1 Waardenburg Syndrome Types 1 and 2
Waardenburg syndrome is characterized by autosomal-dominant transmis-
sion of sensorineural hearing loss accounting for approximately 1.4 to 2%
of congenital hearing loss (Fraser 1976; Partington 1964) and patchy depig-
mentation affecting the skin, hair, and eyes. Neural tube defects or cleft
lip/palate may also be rarely observed (Farrer et al. 1992). The two major
clinical subtypes of Waardenburg syndrome are distinguished by the pres-
ence (type I; WS1; OMIM 193500) or absence (type II; WS2; OMIM 193510)
of dystopia canthorum, which is a lateral displacement of the inner canthi
of the eyes that can be evaluated objectively using the W biometric index
(Farrer et al. 1994; Newton 1989) (Fig. 6.7). Dystopia canthorum in WS1 is
highly penetrant, exceeding 90% (Arias and Mota 1978). Other features of
WS1 include a wide confluent eyebrow, and a high, broad nasal root (Farrer
et al. 1992). Vestibular dysfunction is common but may not be symptomatic
