GJB2 İLİŞKİLİ NON-SENDROMİK İŞİTME KAYBI VARYANTLARININ SPEKTRUMU VE TÜRK TOPLUMUNDAKİ SIKLIKLARI

Abstract

Amaç: İşitme kaybı, çocukluk çağındaki en önemli kronik sağlık sorunlarından biridir ve yaşam kalitesini konuşma, eğitim ve sosyal ilişki sorunlarına yol açarak azaltır. Özellikle non-sendromik işitme kaybında genetik faktörlerin rolü etkilenmiş kişi ve ailelerinin genetik tanı ve genetik danışma aşamalarında doğru yönlendirilmesi açısından kilit bir rol oynar. Bu nedenle, non-sendromik işitme kaybı olan hasta ve ailelerinin önümüzdeki yıllarda genetik tanı ve danışmasına katkıda bulunmak amacıyla, bu çalışmada, 2002-2021 yılları arasında sinirsel tip işitme kaybı tanısı alan hastalardaki GJB2 gen varyantlarını ve sıklıklarını sunmaya çalıştık. Gereç ve Yöntem: GJB2 geninin iki ekzonu, 402 hasta DNA’sında iki ayrı PCR ile çoğaltıldı ve Sanger yöntemi ile dizilendi. Bulgular: Non-sendromik işitme kaybı olan olguların %35’inde (141/402) GJB2 geninde 13 farklı değişim saptadık. Hastaların %53,9’u en yaygın (%59,21) varyant olan c.35delG değişimini homozigot taşırken, %33,3’ü birleşik heterozigot olarak taşıyordu. Yaklaşık %13’ünde ise değişim heterozigot olarak belirlendi. Çalışma grubumuzda en yaygın GJB2 varyantı olan c.35delG değişimini sırasıyla c.71G>A (%6,38), c.-23+1G>A (%3,54) ve c.233delG (%2,48) değişimleri izlemiştir. Keratit-ihtiyoz-sağırlık (KID) ve palmoplantar keratoderma (PPK) sendromu tanılı sekiz hastanın dördünde heterozigot p.Asp50Glu (c.150C>A) değişimi saptandı. Sonuç: Sonuçlarımız, Türkiye’deki non-sendromik işitme kaybı hastalarındaki c.35delG varyantının uzun zamandır bilinen baskınlığını bir kez daha göstermektedir. Ayrıca, tek mutant alelsaptanan hastaların oranı, non-sendromik işitme kaybının alelik heterojenitesi nedeniyle rastlantısal olarak değerlendirilebileceği gibi, digenik kalıtımı da düşündürebilir

Keywords

• Sinirsel tip işitme kaybı
• GJB2 geni
• c.35delG değişimi
• mutasyon sıklığı

GJB2-RELATED NON-SYNDROMIC HEARING LOSS VARIANTS’ SPECTRUM AND THEIR FREQUENCY IN TURKISH POPULATION

Abstract

Objective: Hearing loss (HL) is one of the most prevalent chronic conditions in children and has consequences in speech, language, education, and social functioning which impede the quality of life. Due to the major involvement of the genetic factors in HL, especially non-syndromic HL (NSHL), genetic diagnosis and genetic counseling have a major impact on early management of the affected individuals and their families. Herein, we report the GJB2 gene variants and their frequencies in NSHL cohort at a tertiary health center between 2002-2021 to contribute for the future genetic counseling of Turkish NSHL patients. Materials and Methods: Two exons of the GJB2 gene were amplified in 402 NSHL patients by two separate PCR reactions and sequenced using the Sanger technique. Results: We found 13 different GJB2 variants in 35% (141/402) of the patients with NSHL. 53.9% were homozygous and 33.3% were compound heterozygous for the most common (59.21%) variant, c.35delG. Approximately 13% of the patients were found to carry the variants in the heterozygous state. The most frequent GJB2 variant c.35delG was followed by c.71G>A (6.38%), c.-23+1G>A (3.54%) and c.233delG (2.48%). We found heterozygous p.Asp50Glu (c.150C>A) alteration in four of eight patients with keratitis, ichthyosis, deafness (KID) and palmoplantar keratoderma (PPK) syndrome. Conclusion: Our results further emphasize the well-known prevalance of the GJB2 c.35delG alteration being the most predominant variant in the Turkish NSHL patients. The high rate of mono-allelic state could be considered as coincidental due to high allelic heterogeneity of NSHL, or possibly suggestive for digenic inheritance.

Keywords

• Sensorineural hearing loss
• GJB2 gene
• c.35delG alteration
• mutation frequency

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