Audiological follow-up of non-syndromic sensorineural hearing loss in patients homozygous for the c.35delG mutation in the GJB2 gene

Abstract

The recessive c.35delG mutation in the GJB2 gene is one of the most common mutations associated with non-syndromic sensorineural hearing loss (NSHL). This nonsense mutation knocks out the function of the connexin 26 protein in the inner ear, which is crucial for normal hearing. This hearing loss caused by the c.35delG mutation appears in variable degree, but is generally stable, expressing in moderate to profound level.

We carried out audiological follow-up of individuals homozygous for the recessive mutation c.35delG in the family with NSHL. DNA was extracted from the venous blood of four members of the family affected by NSHL after signing the informed consent. The presence of the c.35delG mutation in the homozygous state was detected using the PCR-RFLP molecular biology technique. The patients were evaluated with pure tone audiometry in order to establish the genotype-phenotype correlation.

Analysis of the audiological data and follow-up of the NSHL in the four affected c.35delG homozygous individuals showed complete penetrance, but variable expressivity. In two sisters of the family, with the same genotype, the expressivity of the NSHL was different from the rest of their other two relatives, two paternal uncles who were profoundly deaf and prelingual. The sisters presented mild, late-onset and progressive hearing loss, affecting frequencies starting at 1000 Hz in an incipient manner and acute in a mild manner, with a gentle slope in tonal audiometry and little displacement in speech audiometry. Both sisters were diagnosed with NSHL after 5 years of age.

Therefore, c.35delG homozygous individuals with postlingual onset NSHL would pass neonatal hearing screening. This would delay diagnosis and treatment of your permanent hearing loss.