Abstract
The prevalence and spectrum of sequence alterations in the SLC26A4 gene, which codes for the anion exchanger pendrin, are population-specific and account for at least 50% of cases of non-syndromic hearing loss associated with an enlarged vestibular aqueduct. A cohort of nineteen patients from Austria with hearing loss and a radiological alteration of the vestibular aqueduct underwent Sanger sequencing of SLC26A4 and GJB2, coding for connexin 26. The pathogenicity of sequence alterations detected was assessed by determining ion transport and molecular features of the corresponding SLC26A4 protein variants. In this group, four uncharacterized sequence alterations within the SLC26A4 coding region were found. Three of these lead to protein variants with abnormal functional and molecular features, while one should be considered with no pathogenic potential. Pathogenic SLC26A4 sequence alterations were only found in 12% of patients. SLC26A4 sequence alterations commonly found in other Caucasian populations were not detected. This survey represents the first study on the prevalence and spectrum of SLC26A4 sequence alterations in an Austrian cohort and further suggests that genetic testing should always be integrated with functional characterization and determination of the molecular features of protein variants in order to unequivocally identify or exclude a causal link between genotype and phenotype.
Highlights
To provide the best possible care for patients affected by hearing loss, and their families, the search for a possible genetic etiology of the disease is mandatory when environmental causes are likely to be excluded
We presented the first characterization of a cohort of Austrian deaf patients with enlarged vestibular aqueduct (EVA)
Biallelic GJB2 and SLC26A4 sequence variations with functional impact could be identified as the genetic determinant of deafness for two and one patient, respectively
Summary
To provide the best possible care for patients affected by hearing loss, and their families, the search for a possible genetic etiology of the disease is mandatory when environmental causes are likely to be excluded. The gap junction-β2 (GJB2) gene, encoding the connexin 26 protein, is the most prevalent gene associated with autosomal recessive non-syndromic hearing loss (ARNSHL) and is responsible for about 50% of cases of genetic deafness in numerous populations [3]. The causal relation between sequence alterations in the SLC26A4 gene and hereditary hearing loss is firmly established [4,5,6,7]. Pathogenic sequence alterations in SLC26A4 are the second most common cause of ARNSHL in most populations [1,8]. In cases that manifest hearing loss, especially congenital sensorineural hearing loss associated with malformations of the inner ear, SLC26A4 variants and their possible clinical implications must be considered in the molecular work-up. The actual pathogenic potential of many SLC26A4 sequence alterations identified by genetic testing remains unclear due to a lack or incomplete knowledge about the function of the corresponding protein product
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
