A causative gene for a highly common type of hearing loss—sensorineural hearing loss, or SNHL—has been identified by a group of Japanese researchers, who report they have successfully replicated the condition using a transgenic mouse. This discovery could potentially be used to develop new treatments for hearing loss.
The gene identified in this study is related to actin—in fact, as many as one third of the causative genes for sensorineural hearing loss that have been discovered so far are genes that encode proteins with functions related to actin. Actin plays an important function in the formation and maintenance of auditory hair and inner ear hair cells. By using a model transgenic mouse to find the compounds that transform actin functions within the inner ear hair cells, scientists could potentially develop new treatments for various strains of hereditary sensorineural hearing loss. The hearing-impaired mouse used in this study could also be a key to discovering treatment for acquired sensorineural hearing loss.
The study findings were published in the October 5, 2016 online edition of EMBO Molecular Medicine. The research group included Associate Professor Takehiko Ueyama, PhD, Kobe University Biosignal Research Center, and Research Fellow Shin-ichiro Kitajiri, PhD, Kyoto University Department of Otolaryngology, Head and Neck Surgery.
One infant in every 1,000 is diagnosed with sensorineural hearing loss, making it an extremely common hereditary disease. It is also estimated that 25-40% of people over age 65 suffer from acquired sensorineural hearing loss (age-related hearing loss), amounting to as many as 10-15 million Japanese people.
Development of a cure or treatments for sensorineural hearing loss have been slow, primarily because the inner ear is a delicate and complex sensory organ that is difficult to research in vitro (outside a living organism). Currently there is no cure for sensorineural hearing loss, and using a hearing aid is still the most effective treatment.
In previous research, scientists discovered approximately 100 causative genes for sensorineural hearing loss. However, there are many unexplained aspects to the process, such as the type of mutation occurring in these genes, and how this causes hearing impairment. In the new study, the research team identified the causative gene for autosomal dominant non-syndromic sensorineural deafness, DFNA1. The causative gene for this disease was first suggested in 1997, but there was doubt regarding its universality and properties.
The research group carried out analysis using next generation sequencing, studying 1,120 patients suffering from hearing impairments of unknown causes. In two families they discovered a novel mutation in the genetic make-up of DIA1 molecule (DIAPH1), which is involved in the lengthening of linear actin filaments. These filaments play an important function in the formation and maintenance of auditory hair and inner ear hair cells. The researchers used biochemical and biological analysis methods on a molecular level to prove that the DIA1 mutant protein created by the mutation is an active form variant that lengthens actin filaments even without external stimulation.
The team engineered a transgenic mouse that manifests this DIA1 mutant protein. They confirmed that the mouse model exhibits traits of sensorineural hearing loss. In the lab, the mice reportedly demonstrated progressive deafness, starting in the upper registers when young, and advancing with age until it covered all registers.
Source: EMBO Molecular Medicine; Kobe University; Kyoto University