Clin Exp Otorhinolaryngol.  2012 Apr;5(Suppl 1):S10-S13.

Genetic Screening of GJB2 and SLC26A4 in Korean Cochlear Implantees: Experience of Soree Ear Clinic

• Shin JW
• Lee SC
• Lee HK
• Park HJ

Abstract

OBJECTIVES
Genetic hearing loss is highly heterogeneous and more than 100 genes are predicted to cause this disorder in humans. In spite of this large genetic heterogeneity, mutations in SLC26A4 and GJB2 genes are primarily responsible for the major etiologies of genetic hearing loss among Koreans. The purpose of this study is to investigate the genetic cause of deafness in Korean cochlear implantees by performing a genetic screening of the SLC26A4 and GJB2 genes.
METHODS
The study cohort included 421 unrelated Korean patients with sensorineural hearing loss (SNHL) and who had received cochlear implants (CI) at Soree Ear Clinic from July 2002 to December 2010. Among 421 CI patients, we studied 230 cases who had received the genetic screening for SLC26A4 or GJB2 genes. Written informed consent was obtained from all participants. All patients had severe to profound, bilateral hearing loss. For 56 patients who showed enlarged vestibular aqueduct on their computed tomography (CT) scan, we analyzed SLC26A4. For 174 CT negative patients, GJB2 gene was sequenced.
RESULTS
For the 56 SLC26A4 patients, 32 (57.1%) had two pathogenic recessive mutations in SLC26A4. A single recessive SLC26A4 mutation was identified in 14 patients (25%). H723R and IVS7-2A>G were the most commonly found mutations, accounting for 60.3% (47/78) and 30.8% (24/78) of the mutated alleles, respectively. For the 174 GJB2 patients, 20 patients (11.5%) had two pathogenic recessive mutations in GJB2. 235delC was the most common mutation, accounting for 43.0% (31/72) of mutant alleles.
CONCLUSION
The two major genes, SLC26A4 and GJB2, contribute major causes of deafness in CI patients. Continuous studies are needed to identify new genes that can cause hearing loss to Korean CI patients.

Keyword

Connexin 26; GJB2 protein; Pendred syndrome; SLC26A4 protein; Cochlear implants

MeSH Terms

Accounting
Alleles
Cochlear Implants
Cohort Studies
Connexins
Deafness
Ear
Genetic Heterogeneity
Genetic Testing
Goiter, Nodular
Hearing Loss
Hearing Loss, Bilateral
Hearing Loss, Sensorineural
Humans
Informed Consent
Vestibular Aqueduct
Connexins

Reference

1. Rennels M, Pickering LK. Sensorineural hearing loss in children. Lancet. 2005; 6. 18-24. 365(9477):2085–2086. PMID: 15964436.

2. Marazita ML, Ploughman LM, Rawlings B, Remington E, Arnos KS, Nance WE. Genetic epidemiological studies of early-onset deafness in the U.S. school-age population. Am J Med Genet. 1993; 6. 15. 46(5):486–491. PMID: 8322805.

3. Lenz DR, Avraham KB. Hereditary hearing loss: from human mutation to mechanism. Hear Res. 2011; 11. 281(1-2):3–10. PMID: 21664957.

4. Park HJ, Hahn SH, Chun YM, Park K, Kim HN. Connexin26 mutations associated with nonsyndromic hearing loss. Laryngoscope. 2000; 9. 110(9):1535–1538. PMID: 10983956.

5. Park HJ, Shaukat S, Liu XZ, Hahn SH, Naz S, Ghosh M, et al. Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness. J Med Genet. 2003; 4. 40(4):242–248. PMID: 12676893.

6. Park HJ, Lee SJ, Jin HS, Lee JO, Go SH, Jang HS, et al. Genetic basis of hearing loss associated with enlarged vestibular aqueducts in Koreans. Clin Genet. 2005; 2. 67(2):160–165. PMID: 15679828.

7. Estivill X, Fortina P, Surrey S, Rabionet R, Melchionda S, D'Agruma L, et al. Connexin-26 mutations in sporadic and inherited sensorineural deafness. Lancet. 1998; 2. 07. 351(9100):394–398. PMID: 9482292.

8. Denoyelle F, Weil D, Maw MA, Wilcox SA, Lench NJ, Allen-Powell DR, et al. Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene. Hum Mol Genet. 1997; 11. 6(12):2173–2177. PMID: 9336442.

9. Morton CC, Nance WE. Newborn hearing screening: a silent revolution. N Engl J Med. 2006; 5. 18. 354(20):2151–2164. PMID: 16707752.

10. Reardon W, Coffey R, Chowdhury T, Grossman A, Jan H, Britton K, et al. Prevalence, age of onset, and natural history of thyroid disease in Pendred syndrome. J Med Genet. 1999; 8. 36(8):595–598. PMID: 10465108.

11. Tsukamoto K, Suzuki H, Harada D, Namba A, Abe S, Usami S. Distribution and frequencies of PDS (SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct: a unique spectrum of mutations in Japanese. Eur J Hum Genet. 2003; 12. 11(12):916–922. PMID: 14508505.

12. Wu CC, Chen PJ, Hsu CJ. Specificity of SLC26A4 mutations in the pathogenesis of inner ear malformations. Audiol Neurootol. 2005; Jul-Aug. 10(4):234–242. PMID: 15905611.

13. Albert S, Blons H, Jonard L, Feldmann D, Chauvin P, Loundon N, et al. SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations. Eur J Hum Genet. 2006; 6. 14(6):773–779. PMID: 16570074.

14. Kelsell DP, Dunlop J, Stevens HP, Lench NJ, Liang JN, Parry G, et al. Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature. 1997; 5. 01. 387(6628):80–83. PMID: 9139825.

15. Zelante L, Gasparini P, Estivill X, Melchionda S, D'Agruma L, Govea N, et al. Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans. Hum Mol Genet. 1997; 9. 6(9):1605–1609. PMID: 9285800.

16. Abe S, Usami S, Shinkawa H, Kelley PM, Kimberling WJ. Prevalent connexin 26 gene (GJB2) mutations in Japanese. J Med Genet. 2000; 1. 37(1):41–43. PMID: 10633133.

17. Kudo T, Ikeda K, Kure S, Matsubara Y, Oshima T, Watanabe K, et al. Novel mutations in the connexin 26 gene (GJB2) responsible for childhood deafness in the Japanese population. Am J Med Genet. 2000; 1. 17. 90(2):141–145. PMID: 10607953.

18. Connexin-deafness homepage [Internet]. Center for Genomic Regulation. 2012. cited 2012 Jan 10. Barcelona: Center for Genomic Regulation;Available from: http://davinci.crg.es/deafness/.

19. 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; 11. 19. 339(21):1500–1505. PMID: 9819448.

20. Brobby GW, Muller-Myhsok B, Horstmann RD. Connexin 26 R143W mutation associated with recessive nonsyndromic sensorineural deafness in Africa. N Engl J Med. 1998; 2. 19. 338(8):548–550. PMID: 9471561.

21. White KR. Early hearing detection and intervention programs: opportunities for genetic services. Am J Med Genet A. 2004; 9. 15. 130A(1):29–36. PMID: 15368492.