Impact of next-generation sequencing on molecular diagnosis of inherited non-syndromic hearing loss

Hearinglossisoneofthemostcommonbirthdefects,withinheritedgeneticdefectsplayanimportantrole,contributingtoabout60%ofdeafnessoccurringininfants.However,hearingimpairmentisgeneticallyheterogeneous,withbothcommonandrareformsoccurringduetomutationsinestimated500genes.Duetothelargenumberandpresumablylowmutationfrequenciesofthosegenes,itwouldbehighlyexpensiveandtime-consumingtoaddressthisissuebyconventionalgene-by-geneSangersequencing.Next-generationsequencingisarevolutionarytechnologythatallowsthesimultaneousscreeningofmutationsinalargenumberofgenes.Itiscosteffectivecomparedtoclassicalstrategiesoflinkageanalysisanddirectsequencingwhenthenumberorsizeofgenesislarge,andthushasbecomeahighlyefficientstrategyforidentifyingnovelcausativegenesandmutationsinvolvedinheritabledisease.Inthisreview,wedescribemajorNGSmethodologiescurrentlyusedforgeneticdisordersandhighlightapplicationsofthesetechnologiesinstudiesofmoleculardiagnosisandthediscoveryofgenesimplicatedinnon-syndromichearingloss.