Genetics of Inner Ear Malformation and Cochlear Nerve Deficiency

Abstract

Studies on genetics of inner ear malformation and cochlear nerve deficiency have been successful in several diseases. Here, we described the current knowledge about the genetics of representative diseases. Among nonsyndromic hearing losses, we reviewed DFNB4 which is caused by mutations in the SLC26A4 and DFN3 which is caused by mutations in POU3F4. Among syndromic hearing losses, we reviewed Waardenburg syndrome, branchio-oto-renal (BOR) syndrome, CHARGE syndrome, Okihiro syndrome, and distal renal tubular acidosis. For chromosomal disorders, trisomy 21 (Down syndrome), trisomy 18, trisomy 13, and 22q11.2 deletion syndrome (DiGeorge syndrome) were reviewed. Although causative genes are identified for only a part of inner ear malformation and cochlear nerve deficiency at present, the situation is likely to change rapidly because of the development of next-generation sequencing technologies. With accumulation of genotype-phenotype information for these auditory disorders, explanation for the causes and mechanisms of hearing loss will become more widely available, planning of medical care will be more effective, and genetic counseling will get more precise.