Munis DÜNDAR, Duygu DUMAN, Mustafa TEKİN, Güney BADEMCİ, Aslı SUBAŞIOĞLU, Aslı SIRMACI, Fehime CARKIT, Mustafa ERKAN, Mehmet Akif SOMDAŞ

Sendromik olmayan ailesel işitme kaybının genetik temelinin araştırılması

Amaç: Toplumda yaklaşık 1 000 canlı doğumda bir görüldüğü bildirilen işitme kaybı en yaygın duyusal işlev bozukluğudur. Bu çalışma ile toplumumuzda ailesel işitme kaybına sıklıkla neden olan genetik değişikliklerin belirlenmesi, ileride işitme kaybına yönelik oluşturulacak genetik tarama programlarına ve hastaların tanı süreçlerine yardımcı bilgiler sunması ve genetik danışmalık hizmetine katkı sağlaması amaçlanmıştır.Gereç ve Yöntemler: Çalışmaya akraba evliliği yapmış, sendromik olmayan işitme kayıplı en az iki çocuğu olan 21 aileden 122 birey alındı. İlk aşamada olgulardan elde edilen DNA örneğinde GJB2 geni dizi analizi ile ve mitokondriyal 12S RNA genindeki m.1555A>G mutasyonu polimeraz zincir reaksiyonu ve elde edilen ürünün restriksiyon enzimi ile kesilerek bant boylarının incelenmesi yaklaşımı kullanılarak hedefe yönelik test ile incelendi. Mutasyon saptanmayan ailelerde "open array" yöntemi kullanılarak TMIE geninde c.250C>T mutasyonu ve işitme kaybına yol açtığı bilinen 11 gen bölgesindeki polimorfik belirteçlere bakılarak (SLC26A4, MYO7A, MYO15A, OTOF, CDH23, TMIE, TECTA, PCDH15, TMC1, TMPRSS3, TMHS) bu gen bölgelerinin işitme kaybıyla birlikte kalıtımı incelendi.Bulgular: GJB2 gen dizi analizinde dört ailede c.[35delG];[35delG], iki ailede c.[35delG];[507C>A], bir ailede c.[35delG];[-23+1G>A] ve bir ailede c.457G>A heterozigot olarak saptandı. "Open array" yöntemi ile yapılan incelemede bir olguda TMIE geninde c.[250C>T];[ 250C>T], bir olguda OTOF, bir olguda TMPRSS3, bir başka olguda ise OTOF, TMPRSS3 ve TMHS genlerinin üçü için otozomal çekinik kalıtım ile uyumlu homozigot bölge taşıdıkları belirlendi. Çıkarımlar: Bu çalışmada sendromik olmayan işitme kayıplı ailelerde daha ileri genetik tetkiklerin yapılması planlandı.

Research of genetic bases of hereditary non-syndromic hearing loss

Aim: Hearing loss is the most common sensory disorder that affects approximately one per 1000 live births. With this project, we aimed to identify gene variants that were common causes of hearing loss in Turkey to contribute to the planning of genetic screening programs for hearing loss, as well as to improve genetic counseling to affected families. Material and Methods: Twenty-one families with at least two affected individuals and parental consanguinity who presented with non-syndromic severe-to-profound sensorineural hearing loss were included in this study. We first screened for mutations in GJB2 and mitochondrial DNA 12S RNA genes. Subsequently, we genotyped the TMIE c.250C>T and SNP markers flanking the SLC26A4, MYO7A, MYO15A, OTOF, CDH23, TMIE, TECTA, PCDH15, TMC1, TMPRSS3, TMHS genes in the remaining twelve families without mutations in GJB2.Results: Screening for mutations in GJB2 gene showed c.[35delG];[35delG] mutation in four families, c.[35delG];[507C>A] mutation in two families, c.[35delG];[-23+1G>A] mutation in one family, and c.457G>A heterozygous mutation in one family. Genotyping SNP markers showed the c.[250C>T];[250C>T] mutation in TMIE in one family. A homozygous region with SNP genotypes was detected with the OTOF gene in one family, the TMPRSS3 gene in another family, and also a homozygous region was detected with TMHS, OTOF, and TMPRSS3 genes in another family. Conclusions: Further research will be required to determine the genetic bases of hearing loss in families with non-syndromic hearing loss.

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