Thyroid gland enlargement (goiter) appears to be primarily dependent on the presence of two mutant alleles of SLC26A4 in pediatric patients, but not in older patients.
Pendred syndrome, a combination of sensorineural deafness, impaired organification of iodide in the thyroid and goitre, results from biallelic defects in pendrin (encoded by SLC26A4), which transports chloride and iodide in the inner ear and thyroid respectively.
Mutations in SLC26A4 cause Pendred syndrome (hearing loss with goiter) or DFNB4 (non-syndromic hearing loss with inner ear malformation, such as enlarged vestibular aqueduct or Mondini deformity).
The first one is named Pendred Syndrome (PS) when deafness is associated with thyroid goiter; the second is called DFNB4, when no other symptoms are present.
Results of this study stress the necessity of considering the analysis of SLC26A4 in molecular diagnosis of deafness especially when phenotypes such as goiter or enlarged vestibular aqueduct are present.
Recessive mutations of the SLC26A4 (PDS) gene on chromosome 7q31 can cause sensorineural hearing loss with goiter (Pendred syndrome) or non-syndromic autosomal recessive hearing loss (DFNB4).
Loss of function mutations in pendrin protein cause Pendred syndrome, a disorder characterized by sensorineural deafness and a partial iodide organification defect that may lead to thyroid goiter.
Clinical characteristics of patients with SLC26A4 mutations were congenital, fluctuating and progressive hearing loss usually associated with vertigo and/or goiter.
We propose using a combination of three parameters to define and diagnose PS: (i) sensorineural deafness with bilateral EVA; (ii) thyroid abnormality comprising goiter and/or hypothyroidism and/or a positive PDT; (iii) biallelic SLC26A4 mutations.
Pendred syndrome is an autosomal recessive disorder characterized by hearing loss and goiter and is caused by bi-allelic mutations (homozygous or compound heterozygous) of the PDS (SLC26A4) gene.
Considering the presence of SLC26A4 mutations and thyroid function, we could identify three sub-groups of patients: group 1, non syndromic EVA (ns EVA, no SLC26A4 mutation and no thyroid dysfunction); group 2, EVA with DFNB4 (single SLC26A4 gene mutation and no thyroid dysfunction); group 3, EVA with Pendred Syndrome (two pathological mutation of SLC26A4 and thyromegaly with thyroid dysfunction).
Whole exome sequencing and/or Sanger sequencing of SLC26A4 in 117 individuals with sensorineural hearing loss with or without inner ear anomalies but not with goiter from Turkey, Iran, and Mexico were performed.