A Novel Mutation of SCL26A4 gene in Turkish Family with Pendred Syndrome

Abstract

Aim: This study aimed to investigate the molecular testing of congenital hearing loss by using next generation sequencing technology. Pendred syndrome (PS) is described by severe bilateral sensorineural hearing loss with goiter. The mutations of SCL26A4 gene can cause PS.

Material and Method: We evaluated the feasibility of target-enrichment and massive parallel sequencing technologies to interrogate all mutations of genes (GJB2, GJB3, GJB6, SLC26A4 and for the mitochondrial mutation A1555G) implicated in NSHL, we performed molecular analyses of 14 NSHL families and patients by using Miseq system (Illumina Inc.). Next-Generation sequencing (NGS) technologies provide specificity, sensitivity and reproducibility at levels sufficient to perform genetic diagnosis of hearing loss.

Results: We found two different mutations in SCL26A4 gene such as F354S and I588T in both consanguineous families as diagnosed with Pendred syndrome and we reported a novel mutation in SCL26A4 gene. We found no mutation in GJB2, GJB3, GJB6 gene and A1555G mtDNA in this study.

Conclusion: These results highlight the benefits using targeted gene panels with NGS technologies in the molecular analysis of nonsyndromic, congenital hearing loss patients. This study assessed the frequency of deafness genes in Turkish children with congenital hearing loss who had been treated with cochlear implantation, and we found a novel mutation (I588T) in SLC26A4 gene.

Key Words: Pendred syndrome, Congenital Hearing Loss, Next-Generation sequencing

Keywords

• -

Pendred Sendromlu Türk Ailede SCL26A4 Geninde Yeni Mutasyon

Abstract

Amaç: Bu çalışmada konjenital işitme kaybının moleküler testini yeni nesil dizileme teknolojisi kullanılarak araştırmayı amaçladık. Pendred sendrome (PS)  yaygın çift taraflı işitme kaybıyla ve guatrla tanımlanmıştır. SCL26A4 gen mutasyonu Pendred sendromuna sebep olur.

Gereç ve Yöntem: Tüm ilgilenilen genlere ait mutasyonların (GJB2, GJB3, GJB6, SLC26A4 genlerinin mutasyonlar ve mitokondrial A155G mutasyonu) incelenmesi masif paralel dizileme teknolojisi ile değerlendirilecektir. 14 NSHL ailenin moleküler genetik analizleri Miseq sistemi kullanılarak gerçekleştirildi. Yeni nesil dizileme teknolojileri, işitme kayıplarının genetik tanısını yapmamızı yeterli düzeyleri spesifite, sensitivite ve üretkenlik sağlar.

Bulgular: Her iki akrabalık olan Pendred sendromu tanılı ailede SCL26A4 geninde F354S ve I588T mutasyonları bulduk ve SCL26A4 geninde yeni mutasyon bildiriyoruz. GJB2, GJB3, GJB6 ve mitokondrial mutasyon saptanmamıştır.

Sonuç: Bu sonuçlar, nonsendromik işitme kaybında moleküler analizlerinde NGS teknolojileri ile hedeflenmiş gen panellerinin avantajlarını vurgulamaktadır. Bu çalışma, kongenital işitme kayıplı kohlear implantlı Türk çocuklarında sağırlık genlerindeki mutasyon sıklığın değerlendirildi ve SCL26A4 geninde I588T mutasyonu saptandı.

Anahtar Kelimeler: Pendred Sendromu, Kongenital İşitme Kaybı, Yeni Nesil Sekanslama

Keywords

• Pendred Sendromu, Kongenital İşitme

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