CLINICAL AND GENETIC SCREENING OF CONGENITAL DEAFNESS

Abstract

Pojavnost prirođenog oštećenja sluha je najmanje 1/1000 novorođene djece. Oko polovice oštećenja sluha je nasljedno, od čega se trećina javlja u sklopu različitih sindroma (sindromska gluhoća), a u dvije trećine slučajeva gluhoća je jedini simptom (nesindromska gluhoća). Smatra se da oko 200 različitih gena uzrokuje pojedine oblike nasljedne gluhoće. Razvoj molekularne genetike omogućio je značajan napredak u detekciji i lokalizaciji ovih gena. Mutacije gena koji kodira sintezu koneksina-26 uzrokuju više od polovice svih slučajeva nasljedne gluhoće. Guilford je 1994. prvi ­opisao autosomno recesivnu nesindromsku gluhoću u lokusu DFNB1 13q11-q12 na 13. kromosomu. U unutarnjem uhu koneksin-26 ima ulogu u recikliranju kalijevih iona od baze dlakavih stanica, preko potpornih stanica i fibroblasta do strije vaskularis, odakle se dalje posebnim kanalima izbacuju u endolimfu. Na tom putu kalijevi ioni prolaze kroz zjapne veze koje izgrađuju koneksin-26, koneksin-30 i koneksin-31. Mutacija u bilo kojem od gena koji kodiraju koneksine mijenja ionski sastav osjetnih stanica i rezultira nastankom gluhoće. Novorođenački probir na oštećenje sluha počeo se razvijati prije četrdesetak godina. Audiološkim probirom metodom evocirane otoakustičke emisije (E-OAE) nastoji se otkriti što više djece s oštećenim sluhom. Djeca u koje se ovom metodom postavi sumnja na oštećenje sluha, upućuju se na automatsko bilježenje evociranih potencijala moždanog debla. U djece s pozitivnim audiološkim nalazom, molekularno-genetsko testiranje danas je moguće za veliki broj gena, ali zbog velike prevalencije mutacija u koneksinskim genima, samo takvo testiranje je šire prihvaćeno. Kombinacija audiološke i molekularno-genetske analize pokazala se komplementarnom, korisnom i praktički primjenjivom.The incidence of congenital hearing impairment is at least 1/1000 newborns. Approximately one half of hearing impairments is hereditary, out of which one third occurs as part of different syndromes (syndromic deafness), and in two thirds of these cases deafness is the only symptom (non-syndromic deafness). It is considered that around 200 ­different genes cause various forms of hereditary deafness. The development of molecular genetics has enabled significant progress in the detection and localization of these genes. Mutations of the gene that encodes the connexin-26 synthesis cause more than half of all hereditary deafness cases. In 1994, Guilford first described autosomal recessive non-syndromic deafness in locus DFNB1 13q11-q12 on the 13th chromosome. In the inner ear, connexin-26 plays a role in the recycling of potassium ions from hairy cells base, through supporting cells and fibroblasts to stria vascularis, from where they are then discharged into endolymph via special channels. On its way, potassium ions pass through gap junctions composed of connexin-26, connexin-30 and connexin-31. Mutation in any of the genes that encode connexins alters the ionic composition of sensory cells and results in the development of deafness. Newborn hearing impairment screening started developing some 40 years ago. Audiologic screening by evoked otoacoustic emission method (E-OAE) aims at detecting as many children as possible with hearing impairment. Children who after using this method are suspected of having hearing impairment are then referred for automated auditory brainstem response. In children with positive audiologic findings, molecular-genetic testing is today possible for a large number of genes, however, due to the significant prevalence of mutations in the connexin genes, only such a testing is more widely accepted. Combination of audiologic and molecular-genetic analysis has proven to be complementary, useful and applicable in practice