B. Coyle et al., MOLECULAR ANALYSIS OF THE PDS GENE IN PENDRED-SYNDROME (SENSORINEURALHEARING-LOSS AND GOITER), Human molecular genetics (Print), 7(7), 1998, pp. 1105-1112
Pendred syndrome is an autosomal recessive disorder characterized by t
he association between sensorineural hearing loss and thyroid swelling
or goitre and is likely to be the most common form of syndromic deafn
ess. Within the thyroid gland of affected individuals, iodide is incom
pletely organified with variable effects upon thyroid hormone biosynth
esis, whilst the molecular basis of the hearing loss is unknown. The P
DS gene has been identified by positional cloning of chromosome 7q31,
within the Pendred syndrome critical linkage interval and encodes for
a putative ion transporter called pendrin, We have investigated a coho
rt of 56 kindreds, all with features suggestive of a diagnosis of Pend
red syndrome. Molecular analysis of the PDS gene identified 47 of the
60 (78%) mutant alleles in 31 families (includes three homozygous cons
anguineous kindreds and one extended family segregating three mutant a
lleles). Moreover, four recurrent mutations accounted for 35 (74%) of
PDS disease chromosomes detected and haplotype analysis would favour c
ommon founders rather than mutational hotspots within the PDS gene. Wh
ilst these findings demonstrate molecular heterogeneity for PDS mutati
ons associated with Pendred syndrome, this study would support the use
of molecular analysis of the PDS gene in the assessment of families w
ith congenital hearing loss.