GJB2 Mutation Distribution in Cases with Nonsyndromic Hearing Loss

Öz

Objective: Hearing loss is the most common sensory defect with a frequency of 1 / 500-1000 in the population. Approximately 25% of hereditary hearing losses are syndromic. In the non-syndromic type, the inheritance pattern is 80% autosomal recessive and the remaining 20% is autosomal dominant. In 20-40% of cases of autosomal recessive nonsyndromic hearing loss (NSI), mutations in the GJB2 gene that encoding Connexin 26 (Cx26), a "tight junction" protein, are thought to be responsible for NSI. In this study, it was aimed to determine the GJB2 mutation spectrum by retrospectively examining the results of 146 cases whose GJB2 molecular analysis was performed between 2012 and 2019 with the suspicion of having autosomal recessive NSI.
Materials and Methods: The exonic and exon-intron splicing regions of the GJB2 gene of 146 patients who presented with the complaint of hearing loss were sequenced by the Sanger sequence analysis method.

Results: Homozygous or combined heterozygous mutations in the GJB2 gene were found in 35 cases. The most common mutation is the c.35delG change in exon 2. The other mutations detected are; c.299_300delAT, c.551G> C, c.334_335delAA, c.109 G> A, c.358_360delGAG, c.71G> A.
Conclusion: GJB2 gene mutations are the most common cause in the etiology of nonsyndromic hearing loss, and sequence analysis of this gene takes the first place in the diagnostic algorithm. In addition, our study contributed to the examination of the mutation spectrum in our country by sharing the mutations detected in the GJB2 gene associated with nonsyndromic hereditary hearing loss.

Anahtar Kelimeler

• Connexin 26
• GJB2
• Hearing loss
• Nonsyndromic

Nonsendromik İşitme Kayıplı Olgularda GJB2 Mutasyon Dağılımı

Öz

Giriş: İşitme kaybı, popülasyonda 1/500-1000 sıklıkta rastlanan en sık görülen duyu kusurudur. Herediter işitme kayıplarının yaklaşık %25’i sendromiktir. Nonsendromik olan kısımda ise kalıtım pateni %80 otozomal resesif, geri kalan %20 otozomal dominant şeklindedir. Otozomal resesif nonsendromik işitme kaybı olgularının %20-40’ında, bir “sıkı bağlantı” proteini olan Connexin 26’yı (Cx26) kodlayan GJB2 genindeki mutasyonlar tablodan sorumlu olarak tespit edilmektedir. Bu çalışmada, otozomal resesif NSI şüphesiyle, 2012-2019 yılları arasında GJB2 moleküler analizi yapılan 146 olgunun sonuçları geriye dönük olarak incelenerek, GJB2 mutasyon spektrumunun belirlenmesi amaçlanmıştır. Gereç ve yöntem: İşitme kaybı şikayeti ile başvuran 146 olgunun GJB2 geninin ekzonik ve ekzon-intron yapışma bölgeleri Sanger dizi analizi yöntemi ile dizilenmiştir. Bulgular: 35 olguda GJB2 geninde homozigot ya da birleşik heterozigot mutasyon saptanmıştır. En sık saptanan mutasyon 2. ekzonda yer alan c.35delG değişikliğidir. Saptanan diğer mutasyonlar ise; c.299_300delAT, c.551G>C, c.334_335delAA, c.109 G>A, c.358_360delGAG, c.71G>A şeklindedir. Sonuç: Nonsendromik işitme kaybının etiyolojisinde en sık olarak GJB2 geni mutasyonları saptanmaktadır ve bu genin dizi analizi tanı algoritmasında ilk sırada yer almaktadır. Ayrıca çalışmamız sonucunda, nonsendromik herediter işitme kaybı ile ilişkili GJB2 genindeki saptanılan mutasyonlar paylaşılarak ülkemizdeki mutasyon spektrumunun incelenmesine katkıda bulunulmuştur.

Anahtar Kelimeler

• GJB2
• Connexin 26
• İşitme kaybı
• Nonsendromik

Kaynakça

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