Abstract
Sensorineural hearing loss (SNHL) is one of the most common features of congenital disorders. There are over a hundred loci associated with SNHL in humans. To date, 53 loci of DFNA, the gene locus responsible for autosomal dominant nonsyndromic SNHL, have been identified and 30 genes have been defined as DFNA-causative. 76 loci of DFNB, the gene locus responsible for autosomal recessive deafness, have been identified, and 55 genes have been defined as DFNB-causative. In addition, 15 mitochondrial DNA mutations associated with SNHL have been discovered. However, it is difficult to detect the causative mutation for each patient with SNHL because of the genetic heterogeneity. Usami et al. have developed an effective screening strategy (Invader assay) for hereditary hearing loss. Using this assay, we can check 46 known mutations in 13 known deafness genes frequently found in Japanese patients with SNHL. Since 2012, this testing has been covered by the social health insurance. We can identify the causative gene mutations in approximately 40% patients with SNHL using the Invader assay. If we cannot identify the mutation by this method, we can add the TaqMan PCR method for checking 55 known mutations in 6 known deafness gene. We can also use massively parallel DNA sequencing (MPS) technology to discover rare causative genes through the multicenter research project. We would need approval from the ethics committee for the multicenter research program. It is important to perform genetic counseling and get written informed consent when conducting genetic testing for congenital SNHL. We can use the results of genetic testing when designing a patient's clinical course of treatment. GJB2 is the gene most frequently associated with congenital SNHL. The c.235delC mutation in this gene, the most frequent allele, is known to be associated with profound deafness. In addition, better speech performance after cochlear implantation can be observed in patients with GJB2-related profound SNHL. If the homozygous c.235delC mutation in the GJB2 gene is identified in patients with profound SNHL, we can recommend cochlear implantation at an early age. Thus, we can select the most suitable clinical course for each patient through genetic counseling by detecting the causative gene mutation.
