Mutations in SLC26A4 cause Pendred syndrome (PS) - hearing loss with goitre - or DFNB4 - non-syndromic hearing loss (NSHL) with inner ear abnormalities such as Enlarged Vestibular Aqueduct (EVA) or Mondini Dysplasia (MD).
Two compound heterozygous mutations (c.215delA/c.2422T-->C and c.387delC/c.1159G-->A) in the thyroid peroxidase gene responsible for congenital goitre and iodide organification defect.
It has been shown that mutations in the SLC26A4 gene are involved in syndromic deafness characterized by congenital sensorineural hearing impairment and goitre (Pendred's syndrome), as well as in congenital isolated deafness (DFNB4), both of which are associated with enlarged vestibular aqueduct (EVA).
The present study confirmed the clinical characteristics of patients with SLC26A4 mutations: congenital, fluctuating, and progressive hearing loss usually associated with vertigo and/or goiter during long-term follow-up.
It has been shown that mutations of the SLC26A4 (PDS) gene were involved in syndromic deafness characterized by congenital sensorineural hearing impairment and goitre (Pendred's syndrome), as well as in congenital isolated deafness (DFNB4).
Chloride uptake studies were made using HEK293-Phoenix cells expressing human wild type SLC26A4 (pendrin) and a mutant (SLC26A4(S28R)) we recently described in a patient with hypothyroidism, goiter and sensorineural hearing loss.
Our study illustrates that if only a single heterozygous SLC26A4/PDS mutation is found in a patient with goiter and deafness, other genetic explanations should be considered.
All patients harbouring mutations in the SLC26A4 gene had goiter and a positive perchlorate discharge test: 3 were slightly hypothyroid and 2 euthyroid.
Mutations in SLC26A4 cause Pendred syndrome, an autosomal-recessive disorder characterized by sensorineural deafness and goiter, and DFNB4, a type of autosomal recessive nonsyndromic deafness in which, by definition, affected persons do not have thyromegaly.
All patients harbouring mutations in the SLC26A4 gene had goiter and a positive perchlorate discharge test: 3 were slightly hypothyroid and 2 euthyroid.
The PDS gene (7q31), responsible for Pendred syndrome (congenital sensorineural hearing loss and goiter), encodes a transmembrane protein known as pendrin.
Thyroid peroxidase (TPO) defects, typically transmitted as autosomal recessive traits, result in hypothyroid goiters with failure to convert iodide into organic iodine.
The combination of all these symptoms suggested the diagnosis of Pendred syndrome (PDS), a disorder characterised by congenital sensorineural hearing loss and a variable degree of thyromegaly due to mutations in the SLC26A4/PDSgene.
Thyroid peroxidase (TPO) defects, typically transmitted as autosomal recessive traits, result in hypothyroid goiters with failure to convert iodide into organic iodine.
Mutations were searched in some of the most likely candidate genes: thyroperoxidase (TPO) in patients with CH goiter, Pax8 and thyrotropin receptor (TSHR) in the other group.
Mutations of the PDS gene, encoding pendrin, are associated with protein mislocalization and loss of iodide efflux: implications for thyroid dysfunction in Pendred syndrome.
TPO transcripts were detected in 7/10 (70%) patients with known metastases of thyroid cancer and in 39 of 110 (36%) patients without metastases (P<0.05), in 15/44 (34%) patients with goitre, in 17/41 (41%) cases with GD and in 4/54 (7.4%) subjects in the control group (P<0.05, controls vs all patients with thyroid disease).