Frequency of gjb2 mutations in families with autosomal recessive non-syndromic hearing loss in Khuzestan province

Abstract

Gubitak sluha je uzrokovan i genetskim i faktorim spoljšnje sredine U tom smislu, više od polovine slučajevje genetski uzrokov no N sledni gubit k sluha se deli n sindromske i ne-sindromske slučajeve Glavni n cin n slediv nj 80 u ne-sindromskim slučajevim je utozomni recesivan, što je pozn to kao autozomni recesivni ne-sindromski gubitak sluha (ARNSHL) I ko je bolest veoma genetski heterogena, gen GJB2 ima najveći efekat. Cilj ovog istraživanja je da se utvrdi uloga GJB2 mutacija i DFNB1 lokusa u grupi porodica sa ARNSHLom u provinciji Huzestan u Iranu. Ova studija je sprovedena u 50 velikih porodica sa ARNSHLom (sa prioritetom od 4 pacijenta) u provinciji Huzestan, u jugozapadnom Iranu. Prvo, u cilju proučavanj GJB2 genskih mutacilja, izvršeno je direktno sekvencir nje u svim porodicama. Osim toga, u porodicama sa negativnim ili heterozigotnim mutacijama u GJB2, linkage analiza obavljena je pomoću STR Short Tandem Repeat) koji se odnose na DFNB1 lokus Genotipovi, vez ni z sv ku porodicu, odredeni su metodom PCR -PAGE. Od 50 porodica sa ARNSHL-om, nakon direktnog sekvenciranja, šest porodica 12 je pok z lo homozigotne mut cije u GJB2 genu Shodno tome, priměceno je da je c 35delG najčešč mutacija 50 u populaciji Štaviše, c 358-360delGAG, c.506G > A, c.71G > mutacije su identifikovane u 3 različite porodice Pored toga, kod DFNB1 lokusa nije bilo povezivanjaza preost le porodice Nisk frekvencija 12 mutacija GJB2 u našoj studiji uk zuje na to d se drugi lokusi i geni trebaju proučavti u cilju razjašnjavnja etiologije ARNSHL-a u ovoj provinciji. © 2018, Serbian Genetics Society. Hearing loss is caused both by genetic and environmental factors. In this sense, more than half of the cases are genetic. Hereditary hearing loss is divided into syndromic and non-syndromic cases. Main pattern of inheritance (80) in non-syndromic cases is autosomal recessive, which is known as autosomal recessive non-syndromic hearing loss (ARNSHL). Although the disease is very genetically heterogeneous, the GJB2 gene has highest effect. The aim of the present research is to determine the role of GJB2 mutations and DFNB1 locus in a group of families with ARNSHL in Khuzestan province of Iran. This study was conducted on 50 large families with ARNSHL (with the priority of 4 patients) in Khuzestan province, southwest Iran. First, in order to study GJB2 gene mutations, direct sequencing was conducted in all families. Besides, in the families with negative or heterozygous mutations in GJB2, linkage analysis was done using STR (Short Tandem Repeat) markers related to DFNB1 locus. Genotypes, related to each family, were determined using PCR-PAGE method. From 50 families with ARNSHL, after direct sequencing, six families (12) showed homozygote mutations in the GJB2 gene. Accordingly, it was observed that c.35delG was the most frequent mutation (50) in the population. Moreover, c.358-360delGAG, c.506G > A, c.71G > A mutations were identified in 3 different families. In addition, no linkage was observed in DFNB1 locus for the remaining families. Low frequency (12) of GJB2 mutations in our study suggests that other loci and genes should be addressed to elucidate the etiology of ARNSHL in this province. © 2018, Serbian Genetics Society.