C. Campbell et al., Pendred syndrome, DFNB4, and PDS/SCL26A4 identification of eight novel mutations and possible genotype-phenotype correlations, HUM MUTAT, 17(5), 2001, pp. 403-411
Mutations in PDS (SLC26A4) cause both Pendred syndrome and DFNB4, two autos
omal recessive disorders that share hearing loss as a common feature. The h
earing loss is associated with temporal bone abnormalities, ranging from is
olated enlargement of the vestibular aqueduct (dilated vestibular aqueduct,
DVA) to Mondini dysplasia, a complex malformation in which the normal coch
lear spiral of 2 1/2 turns is replaced by a hypoplastic coil of 1 1/2 turns
. In Pendred syndrome, thyromegaly also develops, although affected persons
usually remain euthyroid. We identified PBS mutations in the proband of 14
of 47 simplex families (30%) and nine of 11 multiplex families (82%) (P=0.
0023). In all cases, mutations segregated with the disease state in multipl
ex families. Included in the 15 different PDS allele variants we found were
eight novel mutations. The two most common mutations, T416P and IVS8+1G>A,
were present in 22% and 30% of families, respectively. The finding of PDS
mutations in five of six multiplex families with DVA (83%) and four of five
multiplex families with Mondini dysplasia (80%) implies that mutations in
this gene are the major genetic cause of these temporal anomalies. Comparat
ive analysis of phenotypic and genotypic data supports the hypothesis that
the type of temporal bone anomaly may depend on the specific PDS allele var
iant present. Hum Mutat 17:403-411, 2001. (C) 2001 Wiley-Liss, Inc, Inc.