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
References
- Morton NE. Genetic epidemiology of hearing impairment, Ann N Y Acad Sci 1991; 630:26–31.
- Tekin M, Akar N, Cin S. Connexin 26 mutations in the Turkish population: implications for the origin and high frequency of the 35delG mutation in Caucasians, Hum Genet 2001; 108:385-99.
- Walsh T, Shahin H, Elkan-Miller T. Whole exome sequencing and homozygosity mapping identify mutation in the cell polarity protein GPSM2 as the cause of nonsyndromic hearing loss DFNB82, Am J Hum Genet 2010; 87:90-94.
- Gasparini P, Rabionet R, Barbujani G, Melçhionda S, Petersen M, Brøndum-Nielsen K, et al. High carrier frequency of the 35delG deafness mutation in European populations, Eur J Hum Genet 2000;8:19–23.
- Morell RJ, Kim HJ, Hood LJ, Goforth L, Friderici K, Fisher R, et al. Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness, N Engl J Med 1998;339:1500–1505.
- Ohtsuka A, Yuge I, Kimura S, Namba A, Abe S, Van Laer L, et al. GJB2 deafness gene shows a specific spectrum of mutations in Japan, including a frequent founder mutation, Hum Genet. 2003;112:329–333.
- Duman D, Tekin M. Autosomal recessive nonsyndromic deafness genes: a review, Front Biosci 2013;17:2213-2236.
- Maheshwari M, Vijaya R, Ghosh M, Shastri S, Kabra M, Menon PS. Screening of families with autosomal recessive non-syndromic hearing impairment (ARNSHI) for mutations in GJB2 gene:Indian scenario. Am J Med Genet A 2003;120A(2):180–184.
- Battelino S, Replic Lampret B, Zargi M, Podkrajšek KT. Novel connexion 30 and connexion 26 mutational spectrum in patients with progressive sensorineural hearing loss. J Laryngol Otol 2012;126:763-769.
- Denoyelle F, Lina-Granade G, Plauchu H, Bruzzone R, Chaïb H, Lévi-Acobas F, et al. Connexin 26 gene linked to a dominant deafness. Nature 1998;393:319–320.
- Tarkan Ö, Sari P, Demirhan O, Kiroğlu M, Tuncer Ü, Sürmelioğlu Ö, et al. Connexin 26 and 30 mutations in paediatric patients with congenital, nonsyndromic hearing loss treated with cochlear implantation in Mediterranean Turkey. J Laryngol Otol 2013;127:33–37.
- Denise Y, Tekin M, Blanton SH. Next-Generation Sequencing in Genetic Hearing Loss. Genet Test Mol Biomarkers 2013;17(8):581-587.
- Tekin M, Duman T, Boguclu G. Spectrum of GJB2 Mutations in Turkey Comprises Both Caucasian and Oriental Variants: Roles of Parental Consanguinity and Assortative Mating. Human Mutat 2003;21(5):552-3.
- Park HJ, Hahn SH, Chun YM, Park K, Kim HN. Connexin26 mutations associated with nonsyndromic hearing loss. Laryngoscope 2000; 110:1535–1538.
- Van Hauwe P, Everett LA, Coucke P, Scott DA, Kraft ML, Ris-Stalpers C, et al. Two frequent missense mutations in pendred syndrome. Hum Mol Genet 1998;7:1099–1104.
- Coyle B, Reardon W, Herbrick JA, Tsui LC, Gausden E, Lee J, et al. Molecular analysis of the PDS gene in Pendred syndrome. Hum Mol Genet 1998;7:1105–1112
- Busi M, Castiglione A, Taddei Masieri M, Ravani A, Guaran V, Astolfi L, et al. Novel mutations in the SLC26A4 gene. Int J Pediatr Otorhinolaryngol 2012;76:1249-54.
- Yang T, Gurrola JG 2nd, Wu H, Chiu SM, Wangemann P, Snyder PM, et al. Mutations of KCNJ10 together with mutations of SLC26A4 cause digenic non-syndromic hearing loss associated with enlarged vestibular aqueduct syndrome, Am J Hum Genet 2009;84:651–657.
- Shin JW, Lee S, Lee H, Park H. Genetic screening of GJB2 and SCL26A4 in Korean Cochlear Implantees: Experience of Soree Ear Clinic. Clin Exper Otorhinolaryngol 2012;5(1):10-13.
- Yazdanpanahi N, Tabatabaiefar M, Farrokhi E, Abdian N, Bagheri N, Shahbazi S, et al. Mutations in a large Iranian pedigree with Pendred syndrome, Clin Exper Otorhinolaryngol 2014;6(4):201-8.
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 SekanslamaKeywords
References
- Morton NE. Genetic epidemiology of hearing impairment, Ann N Y Acad Sci 1991; 630:26–31.
- Tekin M, Akar N, Cin S. Connexin 26 mutations in the Turkish population: implications for the origin and high frequency of the 35delG mutation in Caucasians, Hum Genet 2001; 108:385-99.
- Walsh T, Shahin H, Elkan-Miller T. Whole exome sequencing and homozygosity mapping identify mutation in the cell polarity protein GPSM2 as the cause of nonsyndromic hearing loss DFNB82, Am J Hum Genet 2010; 87:90-94.
- Gasparini P, Rabionet R, Barbujani G, Melçhionda S, Petersen M, Brøndum-Nielsen K, et al. High carrier frequency of the 35delG deafness mutation in European populations, Eur J Hum Genet 2000;8:19–23.
- Morell RJ, Kim HJ, Hood LJ, Goforth L, Friderici K, Fisher R, et al. Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness, N Engl J Med 1998;339:1500–1505.
- Ohtsuka A, Yuge I, Kimura S, Namba A, Abe S, Van Laer L, et al. GJB2 deafness gene shows a specific spectrum of mutations in Japan, including a frequent founder mutation, Hum Genet. 2003;112:329–333.
- Duman D, Tekin M. Autosomal recessive nonsyndromic deafness genes: a review, Front Biosci 2013;17:2213-2236.
- Maheshwari M, Vijaya R, Ghosh M, Shastri S, Kabra M, Menon PS. Screening of families with autosomal recessive non-syndromic hearing impairment (ARNSHI) for mutations in GJB2 gene:Indian scenario. Am J Med Genet A 2003;120A(2):180–184.
- Battelino S, Replic Lampret B, Zargi M, Podkrajšek KT. Novel connexion 30 and connexion 26 mutational spectrum in patients with progressive sensorineural hearing loss. J Laryngol Otol 2012;126:763-769.
- Denoyelle F, Lina-Granade G, Plauchu H, Bruzzone R, Chaïb H, Lévi-Acobas F, et al. Connexin 26 gene linked to a dominant deafness. Nature 1998;393:319–320.
- Tarkan Ö, Sari P, Demirhan O, Kiroğlu M, Tuncer Ü, Sürmelioğlu Ö, et al. Connexin 26 and 30 mutations in paediatric patients with congenital, nonsyndromic hearing loss treated with cochlear implantation in Mediterranean Turkey. J Laryngol Otol 2013;127:33–37.
- Denise Y, Tekin M, Blanton SH. Next-Generation Sequencing in Genetic Hearing Loss. Genet Test Mol Biomarkers 2013;17(8):581-587.
- Tekin M, Duman T, Boguclu G. Spectrum of GJB2 Mutations in Turkey Comprises Both Caucasian and Oriental Variants: Roles of Parental Consanguinity and Assortative Mating. Human Mutat 2003;21(5):552-3.
- Park HJ, Hahn SH, Chun YM, Park K, Kim HN. Connexin26 mutations associated with nonsyndromic hearing loss. Laryngoscope 2000; 110:1535–1538.
- Van Hauwe P, Everett LA, Coucke P, Scott DA, Kraft ML, Ris-Stalpers C, et al. Two frequent missense mutations in pendred syndrome. Hum Mol Genet 1998;7:1099–1104.
- Coyle B, Reardon W, Herbrick JA, Tsui LC, Gausden E, Lee J, et al. Molecular analysis of the PDS gene in Pendred syndrome. Hum Mol Genet 1998;7:1105–1112
- Busi M, Castiglione A, Taddei Masieri M, Ravani A, Guaran V, Astolfi L, et al. Novel mutations in the SLC26A4 gene. Int J Pediatr Otorhinolaryngol 2012;76:1249-54.
- Yang T, Gurrola JG 2nd, Wu H, Chiu SM, Wangemann P, Snyder PM, et al. Mutations of KCNJ10 together with mutations of SLC26A4 cause digenic non-syndromic hearing loss associated with enlarged vestibular aqueduct syndrome, Am J Hum Genet 2009;84:651–657.
- Shin JW, Lee S, Lee H, Park H. Genetic screening of GJB2 and SCL26A4 in Korean Cochlear Implantees: Experience of Soree Ear Clinic. Clin Exper Otorhinolaryngol 2012;5(1):10-13.
- Yazdanpanahi N, Tabatabaiefar M, Farrokhi E, Abdian N, Bagheri N, Shahbazi S, et al. Mutations in a large Iranian pedigree with Pendred syndrome, Clin Exper Otorhinolaryngol 2014;6(4):201-8.
Details
| Primary Language | English |
|---|---|
| Journal Section | Original Articles |
| Authors | |
| Publication Date | June 30, 2015 |
| Submission Date | April 8, 2015 |
| Published in Issue | Year 2015 Volume: 6 Issue: 22 |
