Whilst these findings demonstrate molecular heterogeneity for PDS mutations associated with Pendred syndrome, this study would support the use of molecular analysis of the PDS gene in the assessment of families with congenital hearing loss.
Molecular analysis of the PDS gene is useful to make a definite diagnosis in familial and sporadic cases with Pendred's syndrome, and will be helpful for determining the true prevalence of this disorder.
The present results question the sensitivity of the perchlorate test for the diagnosis of Pendred syndrome and support the use of a molecular analysis of the PDS gene in the assessment of individuals with severe to profound congenital hearing loss associated with inner ear morphological anomaly even in the absence of a thyroid goiter.
Malformations of the inner ear, specifically enlargement of the vestibular aqueduct, are common in Pendred syndrome and mutations in the PDS (Pendred Syndrome) gene have been recorded in patients presenting with deafness and vestibular aqueduct dilatation only, without other features of Pendred syndrome.
Functional differences of the PDS gene product are associated with phenotypic variation in patients with Pendred syndrome and non-syndromic hearing loss (DFNB4).
It is caused by mutations in the Pendred's syndrome (PDS) gene that encodes pendrin, a chloride/iodide transporter expressed in the thyroid, the inner ear, and the kidney.
Consistent with the Pendred's syndrome phenotype, which is characterized by thyroid dysfunction associated to deafness, PDS expression has been demonstrated in the thyroid and in the inner ear.
Sequence analysis of the PDS gene performed with DNA from the two relatives with Pendred's syndrome revealed the presence of a deletion of thymidine 279 in exon 3, a point mutation that results in a frameshift and a premature stop codon at codon 96 in the pendrin molecule.
Mutations in the PDS gene and the consequent impaired function of pendrin leads to the classic phenotype of Pendred syndrome, i.e. dyshormonogenic goiter and congenital sensorineural hearing loss.
Mutations of the PDS gene, encoding pendrin, are associated with protein mislocalization and loss of iodide efflux: implications for thyroid dysfunction in Pendred syndrome.
The PDS gene (7q31), responsible for Pendred syndrome (congenital sensorineural hearing loss and goiter), encodes a transmembrane protein known as pendrin.
PDS is often associated with enlarged endolymphatic duct and sac (EEDS), and recently, PDS gene mutations have been reported even in those patients with EEDS without classic Pendred syndrome.
Recessive mutations of PDS gene are the common causes of Pendred syndrome and non-syndromic hearing loss associated with temporal bone abnormalities ranging from isolated enlargement of the vestibular aqueduct (EVA) to Mondini dysplasia.