Emqn best practice guidelines for diagnostic testing of mutations causing non-syndromic hearing impairment at the dfnb1 locus

摘要

Hearing impairment is the most common sensory disorder, affecting one in every 500-1000 newborns (http://hearing. screening.nhs.ukationalprog). It is estimated that about half of these have a genetic cause, whereas the other half are caused by environmental factors, such as rubella or CMV infection during pregnancy, factors associated with prematurity or ototoxic medication. In most genetic cases, the inheritance pattern is autosomal recessive (80%), but also autosomal dominant (17%), X-linked (2-3%) and mitochondrial (<1%) inheritance has been described. In about 30% of cases, additional clinical and/or physical features lead to a syndrome diagnosis, but in the remaining 70% the only finding is hearing impairment in otherwise healthy people. Non-syndromic hearing loss is genetically very heterogeneous, with over 150 associated loci and >60 identified causative genes (http:// hereditaryhearingloss.org/). Remarkably, defects in one locus {DFNB1) account for up to 50% of cases in many populations, which makes this the most common cause of non-syndromic, prelingual hearing impairment and deafness.