Deafness, Autosomal Recessive 61 (DFNB61) via the SLC26A5 Gene

Nonsyndromic hearing loss is characterized by difficulty or inability to hear that is not associated with any visible defects involving the external ear, other organs, or any other medical condition. Nonsyndromic hearing loss may be associated with abnormalities involving the middle ear and/or the inner ear (Ciuman 2013; Dodson et al. 2011; Hilgert et al. 2009). At least 70% of cases involving hearing loss are nonsyndromic (Van Camp et al. 1997).

Nonsyndromic hearing loss and deafness due to pathogenic variants in the SLC26A5 gene involves congenital to prelingual, bilateral, moderate to severe sensorineural hearing impairment. No vestibular abnormalities are present (Mutai et al. 2013).

DFNB61 is an autosomal recessive hearing disorder that is caused by pathogenic sequence variants in the solute carrier family 26 member 5 (SLC26A5) gene, which is located on chromosome 7q22.1. The SLC26A5 gene spans 97.5 kb and consists of 18 coding exons that produce a 744 amino acid protein. The SLC26A5 protein (commonly called prestin) is also referred to as the motor protein of cochlear outer hair cells for the role it plays in quickly altering cell length in response to changes in membrane potential triggered by incoming sound waves (Zheng et al. 2000; Birke and Javelle 2016). Two Japanese sisters with sensorineural hearing loss were found to be compound heterozygotes for a missense and nonsense variant in the SLC26A5 gene (Mutai et al. 2013).

In a study of 1,119 patients with hearing loss in which 440 patients received a genetic diagnosis, only two pathogenic variants in SLC26A5 were detected (Sloan-Heggen et al. 2016). In total, only 6 variants in SLC26A5 have been reported as pathogenic for hearing loss (Human Gene Mutation Database). Analytical sensitivity should be high because all reported variants are detectable by sequencing.

No deletion or duplication variants associated with SLC26A5 have been reported as pathogenic for hearing loss.

This test provides full coverage of all coding exons of the SLC26A5 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).