Tekin, MustafaDuman, Duygu Akçayöz2022-06-022022-06-022005http://hdl.handle.net/20.500.12575/80941Gene Analysis in a Group of Turkish PatientsCongenital or prelingual onset hearing loss affects 1 in 1000 newborns, half of which isconsidered to be caused by genetic factors. Mutations in a number of genes manifestingthemselves with autosomal recessive inheritance are believed to be responsible inapproximately 80% of genetic cases. About 30 % of the hereditary hearing loss also haveother clinical signs associated with deafness. Pendred syndrome , initially described asdeafness and goiter, has been reported as the most common form of syndromic hearing loss.Mutations in the SLC26A4 gene, encoding for a chloride-iodide transporter protein, pendrin,are responsible for the syndrome. Although four different mutations in SLC26A4 were foundin two Turkish families, a systematic search for the frequency of this syndrome or mutationanalysis in the Turkish population has not been reported previously. In this study we aimed todetermine the frequency of probands with deafness and goiter among Turkish people withhearing loss, and also to screen for SLC26A4 mutations in cases with Pendred syndrome. Asa consequence of our results we hoped to provide better genetic counselling to ourpopulation with hearing loss.A total of 333 probands with pre-lingual-onset severe to profound sensorineural hearing losscoming from reportedly unrelated 293 families, were included in the study after exclusion ofcases where unequivocal evidence was present for an environmental etiology. All patientswere found to be negative for GJB2 and mitochondrial A1555G mutations. Goiter was notedin 11 probands (3.3%) coming from eight unrelated families (3%). None of these studentshad been diagnosed with Pendred syndrome before. Genomic DNA was extracted by aconventional phenol- chloroform method. The SLC26A4 gene was screened with PCR-SSCPprotocols. Samples showing band changes were sequenced on an automated DNAsequencer.Mutation analyzes revealed three different mutations, c.2168A>G (p.His723Arg), c.716T>A(p.Val239Asp) and c.1341delG in homozygous state in probands coming from three familieswith more than one affected member.The prevalence of goiter in the Turkish children from the school of deaf is 2.8 %. In thisstudy following the mutation anaysis Pendred syndrome was definitively diagnosed in five outof 333 (1.5%) probands or in other words in three out of 293 independent families (1%) inTurkey. Our results and those of two previous reports suggest that the mutational spectrumof Pendred syndrome in the Turkish population is heterogeneous and private mutations areresponsible for the disorder in unrelatedl families. Therefore, screening of the whole gene isrecommended in Turkish families with Pendred syndrome originating from Turkey.Key words: Goiter, Hearing loss, Pendred syndrome, SLC26A4, Turkish population.trBiyofizikmasterThesis