Cochleo-vestibular phenotype in patients with pathogenic variations in the ACTG1 gene

This study aimed to investigate the prevalence of pathogenic, likely pathogenic, and variants of unknown significance in the ACTG1 gene among families with suspected bilateral sensorineural hearing loss of genetic origin. Additionally, the research aimed to elucidate the cochleovestibular phenotype of individuals carrying these variants.

A cohort of 365 unrelated families with sensorineural hearing loss participated in this study. Genetic analysis was conducted using Next-Generation Sequencing (NGS).

The study identified c.94C>A and c.721G>A pathogenic variants in heterozygosity in the ACTG1 gene among three probands. Two of these cases exhibited an autosomal dominant inheritance pattern, while the third was a de novo variant. Additionally, three other family members underwent genetic and audiological evaluations. Onset of hearing loss typically occurred between the first and second decades of life, initially affecting high frequencies and gradually extending to all frequencies. Treatment with hearing aids yielded favourable outcomes in all cases.

Pathogenic variants in the ACTG1 gene were found to be rare in the studied population. Nonetheless, these variants should be considered in families presenting with postlingual bilateral sensorineural hearing loss, particularly when high-frequency hearing loss progressively worsens to profound levels.