Prevalence of the IVS1(+1)G→A and 35delG mutations in the GJB2 gene of Turkish patients with nonsyndromic hearing loss

GJB2, iç kulaktaki potasyum geri dönüşüm yolunun bir bileşeni olarak varsayılan koneksin 26, ara bağlantı proteinini, kodlar. GJB2 genindeki mutasyonlar tarafından ortaya çıkan bu ara bağlantıların kayıp veya hasarı, tüy hücrelerinden endolimft eki destek hücre bağlantısına doğru olan potasyum hareketini bozarak işitme kaybına yol açar. Kodon 10’da 30-35. nükleotit pozisyonları arasındaki 6 guanin nükleotit dizisinden bir guanine nükleotidinin delesyonu olan bir mutasyon, sporadik hastalar ve otozomal resesif ailelerde GJB2’nin alelik varyantlarına neden olan en yaygın sağırlık sebebidir. GJB2 genindeki mutasyonlar otozomal resesif sensörinöral işitme kaybının en yaygın nedenlerinden biridir. 35 del G mutasyonu, tanımlanan mutasyonların 2/3 oranından daha fazla oranda yer alır. Bu çalışma kapsamında otozomal resesif, prelingual sendromik olmayan işitme kayıplı, birbirinden bağımsız 173 Türk hasta arasında özellikle connexin 26 (GJB2) connexin 30 (GJB6) ve 12srRNA genlerindeki yaygın mutasyonlar, Polimeraz Zincir Reaksiyonu Restriksiyon Parça Uzunluk Polimorfi zmi (PZR-RFLP), SSCP ve dizi analiz yöntemleri ile araştırılmıştır. İki farklı mutasyon ve bir polimorfizm, (35delG, IVS1+(1)G→A mutasyonları ve V153I polimorfizmi) şiddetli ve ağır tipte işitme kaybına sahip hastalarda bulunmuştur. 35delG mutasyonu Türk hastalarımız arasında en yaygın patojenik allel olarak tespit edilmiştir ve tüm mutant GJB2 allellerin yaklaşık % 50’sinde yer almaktadır. Cx26 geninde 35delG ve IVS1+1G→A mutasyonları sırasıyla % 16,47 ve % 4,33 toplam allel frekansıyla tespit edilmiştir. Hastalarımız arasında V153 polimorfizmi % 3,47 allel frekansı ile heterozigot halde bulunmuştur. Diğer taraft an Cx30 genindeki 342-kb delesyon ve 12 srRNA genindeki mitokondriyal (mt)1555A→G mutasyonları çalışılan hastalar arasında bulunamamıştır.

Sendromik olmayan işitme kayıplı Türk hastaların GJB2 genindeki IVS1(+1)G→A ve 35delG mutasyonlarının yaygınlığı

GJB2 encodes connexin 26, a gap junction protein that is assumed to be a component of the potassium recycling pathway in the inner ear. Loss or malfunction of these gap junctions, as might be refl ected by mutations in GJB2, may disrupt potassium movement from the hair cells through the supporting cell network to the endolymph, leading to hearing impairment. One mutation, the deletion of 1 guanosine residue from a stretch of 6 between nucleotide positions 30 and 35 (35delG) at codon 10, is the most common deafness-causing allelic variant of GJB2 in sporadic patients and autosomal recessive families. Mutations in the GJB2 gene represent the most common cause of autosomal recessive, sensorineural hearing loss. The 35delG mutation accounts for more than two-thirds of identifi ed mutations. In this study, mutations, especially in the connexin 26 (GJB2), connexin 30 (GJB6), and 12srRNA genes, among 173 unrelated patients with prelingual nonsyndromic autosomal recessive deafness were screened and investigated by using the polymerase chain reactionbased restriction fragment length polymorphism (PCR-based RFLP), single-strand conformation polymorphism (SSCP), and sequence analysis methods. In patients with severe to profound hearing loss, 2 diff erent mutations and 1 polymorphism (35delG and IVS1(+1)G→A mutations and V153I polymorphism) were found. The 35delG mutation was detected as the most common pathogenic allele among the Turkish patients and accounted for 50% of all mutant GJB2 alleles. The 35delG and IVS1+1G→A mutations in the Cx26 gene were detected with total allele frequencies of 16.47% and 4.33%, respectively, and the V153 polymorphism was found in a heterozygous state at an allele frequency of 3.47%. However, the 342-kb deletion in the Cx30 gene and mitochondrial (mt)1555A→G in the 12srRNA gene mutations could not be detected among the studied patients.

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