Postlingual late-onset progressive sensorineural hearing loss can be congenital or hereditary. Clinical application of next-generation sequencing (NGS) has enabled identification of the genes responsible for this disorder, which had hitherto proved impossible. TMPRSS3 is one of such genes.
There are two types of TMPRSS3 mutations: DFNB8, associated with moderate post lingual hearing loss, and DFNB10, associated with congenital hearing loss. We were able to identify a mutation of the TMPRSS3 gene, which was proven to be homozygous by NGS, in a patient with progressive sensorineural hearing loss. This patient is the first reported case of progressive mid- to low-frequency sensorineural hearing loss associated with mutation of the TMPRSS3 gene.
An 8-year-old girl was referred to our clinic for bilateral sensorineural hearing loss with a valley-type pattern at around 1 kHz, despite the absence of any detected abnormalities during medical checkups in infancy and childhood. The low-tone hearing loss worsened in the left ear at age 10, and progressed to mid- to low-frequency hearing loss in both ears at the age of 23 years. She was assessed as mutation negative (GJB2, SLC26A4, and Mt1555A>G) by direct sequencing. However, subsequent analysis of NGS data revealed a homozygous mutation of the TMPRSS3 gene, and it was found that her parents were carriers.
Most patients with hearing loss due to TMPRSS3 gene mutation exhibit progressive high-tone hearing loss and then gradually develop steep high-tone sensorineural hearing loss. However, this patient experienced hearing loss with a valley-type pattern followed by low-tone hearing loss, which has not been reported previously. It is considered that genetic testing using NGS is useful for definitive diagnosis of sensorineural hearing loss of unknown etiology detected during adulthood in patients with progressive sensorineural hearing loss, as in the present patient.
