Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
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Carrier frequency of SLC26A4 mutations causing inherited deafness in the Korean population

  • Kim, Hyogyeong (Department of Laboratory Medicine, Seoul Medical Science Institute, Seoul Clinical Laboratories) ;
  • Lim, Hwan-Sub (Department of Laboratory Medicine, Kwandong University College of Medicine) ;
  • Ryu, Jae-Song (Department of Laboratory Medicine, Seoul Medical Science Institute, Seoul Clinical Laboratories) ;
  • Kim, Hyun-Chul (Department of Laboratory Medicine, Seoul Medical Science Institute, Seoul Clinical Laboratories) ;
  • Lee, Sanghoo (Department of Laboratory Medicine, Seoul Medical Science Institute, Seoul Clinical Laboratories) ;
  • Kim, Yun-Tae (Department of Laboratory Medicine, Seoul Medical Science Institute, Seoul Clinical Laboratories) ;
  • Kim, Young-Jin (Department of Laboratory Medicine, Seoul Medical Science Institute, Seoul Clinical Laboratories) ;
  • Lee, Kyoung-Ryul (Department of Laboratory Medicine, Seoul Medical Science Institute, Seoul Clinical Laboratories) ;
  • Park, Hong-Joon (Department of Otorhinolaryngology, Soree Ear Clinic) ;
  • Han, Sung-Hee (Department of Laboratory Medicine, Seoul Medical Science Institute, Seoul Clinical Laboratories)
  • Received : 2014.06.30
  • Accepted : 2014.10.31
  • Published : 2014.12.31
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Abstract

Purpose: The mutation of the SLC26A4 gene is the second most common cause of congenital hearing loss after GJB2 mutations. It has been identified as a major cause of autosomal recessive nonsyndromic hearing loss associated with enlarged vestibular aqueduct and Pendred syndrome. Although most studies of SLC26A4 mutations have dealt with hearing-impaired patients, there are a few reports on the frequency of these mutations in the general population. The purpose of this study was to evaluate the prevalence of SLC26A4 mutations that cause inherited deafness in the general Korean population. Materials and Methods: We obtained blood samples from 144 Korean individuals with normal hearing. The samples were subjected to polymerase chain reaction to amplify the entire coding region of the SLC26A4 gene, followed by direct DNA sequencing. Results: Sequencing analysis of this gene identified 5 different variants (c.147C>G, c.225G>C, c.1723A>G, c.2168A>G, and c.2283A>G). The pathogenic mutation c.2168A>G (p.H723R) was identified in 1.39% (2/144) of the subjects with normal hearing. Conclusion: These data provide information about carrier frequency for SLC26A4 mutation-associated hearing loss and have important implications for genetic diagnostic testing for inherited deafness in the Korean population.

Keywords

References

  1. Fortnum HM, Summerfield AQ, Marshall DH, Davis AC, Bamford JM. Prevalence of permanent childhood hearing impairment in the United Kingdom and implications for universal neonatal hearing screening: questionnaire based ascertainment study. BMJ 2001;323:536-40. https://doi.org/10.1136/bmj.323.7312.536
  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;46:486-91. https://doi.org/10.1002/ajmg.1320460504
  3. Hilgert N, Smith RJ, Van Camp G. Forty-six genes causing nonsyndromic hearing impairment: which ones should be analyzed in DNA diagnostics? Mutat Res 2009;681:189-96. https://doi.org/10.1016/j.mrrev.2008.08.002
  4. Han SH, Park HJ, Kang EJ, Ryu JS, Lee A, Yang YH, et al. Carrier frequency of GJB2 (connexin-26) mutations causing inherited deafness in the Korean population. J Hum Genet 2008;53:1022-8. https://doi.org/10.1007/s10038-008-0342-7
  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;40:242-8. https://doi.org/10.1136/jmg.40.4.242
  6. Kenneson A, Van Naarden Braun K, Boyle C. GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: a HuGE review. Genet Med 2002;4:258-74. https://doi.org/10.1097/00125817-200207000-00004
  7. Scott DA, Wang R, Kreman TM, Andrews M, McDonald JM, Bishop JR, et al. Functional differences of the PDS gene product are associated with phenotypic variation in patients with Pendred syndrome and non-syndromic hearing loss (DFNB4). Hum Mol Genet 2000;9:1709-15. https://doi.org/10.1093/hmg/9.11.1709
  8. Pryor SP, Madeo AC, Reynolds JC, Sarlis NJ, Arnos KS, Nance WE, et al. SLC26A4/PDS genotype-phenotype correlation in hearing loss with enlargement of the vestibular aqueduct (EVA): evidence that Pendred syndrome and non-syndromic EVA are distinct clinical and genetic entities. J Med Genet 2005;42:159-65. https://doi.org/10.1136/jmg.2004.024208
  9. Fraser GR. Association of congenital deafness with goitre (Pendred's syndrome) a study of 207 families. Ann Hum Genet 1965;28:201-49.
  10. Alasti F, Van Camp G, Smith RJH. Pendred Syndrome/DFNB4. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Stephens K, eds. $GeneReviews^{(R)}$ [Internet]. Seattle (WA): University of Washington, Seattle, 1993-2014.
  11. Scott DA, Wang R, Kreman TM, Sheffield VC, Karniski LP. The Pendred syndrome gene encodes a chloride-iodide transport protein. Nat Genet 1999;21:440-3. https://doi.org/10.1038/7783
  12. Wangemann P, Nakaya K, Wu T, Maganti RJ, Itza EM, Sanneman JD, et al. Loss of cochlear HCO3- secretion causes deafness via endolymphatic acidification and inhibition of Ca2+ reabsorption in a Pendred syndrome mouse model. Am J Physiol Renal Physiol 2007;292:F1345-53. https://doi.org/10.1152/ajprenal.00487.2006
  13. Chen N, Tranebjaerg L, Rendtorff ND, Schrijver I. Mutation analysis of SLC26A4 for Pendred syndrome and nonsyndromic hearing loss by high-resolution melting. J Mol Diagn 2011;13:416-26. https://doi.org/10.1016/j.jmoldx.2011.03.003
  14. Ito T, Choi BY, King KA, Zalewski CK, Muskett J, Chattaraj P, et al. SLC26A4 genotypes and phenotypes associated with enlargement of the vestibular aqueduct. Cell Physiol Biochem 2011;28:545-52. https://doi.org/10.1159/000335119
  15. Friedman TB, Griffith AJ. Human nonsyndromic sensorineural deafness. Annu Rev Genomics Hum Genet 2003;4:341-402. https://doi.org/10.1146/annurev.genom.4.070802.110347
  16. Lee KY, Choi SY, Bae JW, Kim S, Chung KW, Drayna D, et al. Molecular analysis of the GJB2, GJB6 and SLC26A4 genes in Korean deafness patients. Int J Pediatr Otorhinolaryngol 2008;72:1301-9. https://doi.org/10.1016/j.ijporl.2008.05.007
  17. Song MJ, Lee ST, Lee MK, Ji Y, Kim JW, Ki CS. Estimation of carrier frequencies of six autosomal-recessive Mendelian disorders in the Korean population. J Hum Genet 2012;57:139-44. https://doi.org/10.1038/jhg.2011.144
  18. 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;67:160-5.
  19. Hu H, Wu L, Feng Y, Pan Q, Long Z, Li J, et al. Molecular analysis of hearing loss associated with enlarged vestibular aqueduct in the mainland Chinese: a unique SLC26A4 mutation spectrum. J Hum Genet 2007;52:492-7. https://doi.org/10.1007/s10038-007-0139-0
  20. 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;7:1099-104. https://doi.org/10.1093/hmg/7.7.1099
  21. Bogazzi F, Russo D, Raggi F, Ultimieri F, Berrettini S, Forli F, et al. Mutations in the SLC26A4 (pendrin) gene in patients with sensorineural deafness and enlarged vestibular aqueduct. J Endocrinol Invest 2004;27:430-5. https://doi.org/10.1007/BF03345286
  22. Pourova R, Janousek P, Jurovcik M, Dvorakova M, Malikova M, Raskova D, et al. Spectrum and frequency of SLC26A4 mutations among Czech patients with early hearing loss with and without Enlarged Vestibular Aqueduct (EVA). Ann Hum Genet 2010;74:299-307. https://doi.org/10.1111/j.1469-1809.2010.00581.x
  23. Chen Y, Tudi M, Sun J, He C, Lu HL, Shang Q, et al. Genetic mutations in non-syndromic deafness patients of Uyghur and Han Chinese ethnicities in Xinjiang, China: a comparative study. J Transl Med 2011;9:154. https://doi.org/10.1186/1479-5876-9-154
  24. 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;11:916-22. https://doi.org/10.1038/sj.ejhg.5201073
  25. Dai P, Yuan Y, Huang D, Zhu X, Yu F, Kang D, et al. Molecular etiology of hearing impairment in Inner Mongolia: mutations in SLC26A4 gene and relevant phenotype analysis. J Transl Med 2008;6:74. https://doi.org/10.1186/1479-5876-6-74
  26. Wang QJ, Zhao YL, Rao SQ, Guo YF, Yuan H, Zong L, et al. A distinct spectrum of SLC26A4 mutations in patients with enlarged vestibular aqueduct in China. Clin Genet 2007;72:245-54. https://doi.org/10.1111/j.1399-0004.2007.00862.x
  27. Hu X, Liang F, Zhao M, Gong A, Berry ER, Shi Y, et al. Mutational analysis of the SLC26A4 gene in Chinese sporadic nonsyndromic hearing-impaired children. Int J Pediatr Otorhinolaryngol 2012;76:1474-80. https://doi.org/10.1016/j.ijporl.2012.06.027
  28. Choi BY, Stewart AK, Nishimura KK, Cha WJ, Seong MW, Park SS, et al. Efficient molecular genetic diagnosis of enlarged vestibular aqueducts in East Asians. Genet Test Mol Biomarkers 2009;13:679-87. https://doi.org/10.1089/gtmb.2009.0054
  29. Shin JW, Lee SC, Lee HK, Park HJ. Genetic screening of GJB2 and SLC26A4 in Korean cochlear implantees: experience of soree ear clinic. Clin Exp Otorhinolaryngol 2012;5(Suppl 1):S10-3. https://doi.org/10.3342/ceo.2012.5.S1.S10
  30. Moeller MP. Early intervention and language development in children who are deaf and hard of hearing. Pediatrics 2000;106:E43. https://doi.org/10.1542/peds.106.3.e43
  31. Yoshinaga-Itano C, Sedey AL, Coulter DK, Mehl AL. Language of early- and later-identified children with hearing loss. Pediatrics 1998;102:1161-71. https://doi.org/10.1542/peds.102.5.1161