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Table of Contents
Vol. 10, No. 4, 2005
Issue release date: July–August 2005
Audiol Neurotol 2005;10:234–242
(DOI:10.1159/000085825)

Specificity of SLC26A4 Mutations in the Pathogenesis of Inner Ear Malformations

Wu C.-C. · Chen P.-J. · Hsu C.-J.
aDepartment of Otolaryngology, National Taiwan University Hospital, and bGraduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

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Abstract

The traditional hypothesis concerning the pathogenesis of inner ear malformations holds that various types of malformations represent different stages of developmental arrest during embryogenesis. In order to verify this hypothesis, we surveyed mutations in the SLC26A4(PDS) gene, which were documented to cause enlarged vestibular aqueduct (EVA) and Mondini’s dysplasia (incomplete partition of the cochlea), in 35 families with various types of inner ear malformations. In 25 families, the probands showed EVA or Mondini’s dysplasia as the main temporal bone abnormalities, whereas the probands in the remaining 10 families revealed other types of malformations. In total, 7 mutated SLC26A4 alleles, including 6 missense mutations (A372V, A387V, T410M, S448L, T721M, and H723R) and 1 splice site mutation (IVS7-2A→G), were detected. All mutated alleles segregated the malformations of EVA and Mondini’s dysplasia, whereas no mutated alleles were found in the 10 probands with other types of malformations. SLC26A4 mutations were found in 22 of the 25 probands with EVA or Mondini’s dysplasia, indicating that these might be specific to the development of Mondini’s dysplasia and EVA. It is inferred that the pathogenetic mechanisms of the various malformations essentially differ, although their radiological findings appear to follow a continuum of morphological changes.



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References

  1. Antonelli PJ, Varela AE, Mancuso AA: Diagnostic yield of high-resolution computed tomography for pediatric sensorineural hearing loss.Laryngoscope 1999;109:1642–1647.
  2. Blons H, Feldmann D, Duval V, Messaz O, Denoyelle F, Loundon N, Sergout-Allaoui A, Houang M, Duriez F, Lacombe D, Delobel B, Leman J, Catros H, Journel H, Drouin-Garraud V, Obstoy MF, Toutain A, Oden S, Toublanc JE, Couderc R, Petit C, Garabedian EN, Marlin S: Screening of SLC26A4 (PDS) gene in Pendred’s syndrome: A large spectrum of mutations in France and phenotypic heterogeneity. Clin Genet 2004;66:333–340.
  3. Campbell C, Cucci RA, Prasad S, Green GE, Edeal JB, Galer CE, Karniski LP, Sheffield VC, Smith RJ: Pendred syndrome, DFNB4, and PDS/SLC26A4. Identification of eight novel mutations and possible genotype-phenotype correlations. Hum Mutat 2001;17:403–411.
  4. Emmett JR: The large vestibular aqueduct syndrome. Am J Otol 1985;6:387–415.
  5. Everett LA, Glaser B, Beck JC, Idol JR, Buchs A, Heyman M, Adawi F, Hazani E, Nassir E, Baxevanis AD, Sheffield VC, Green ED: Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nat Genet 1997;17:411–422.
  6. Everett LA, Morsli H, Wu DK, Green ED: Expression pattern of the mouse ortholog of the Pendred’s syndrome gene (Pds) suggests a key role for pendrin in the inner ear. Proc Natl Acad Sci USA 1999;96:9727–9732.
  7. Everett LA, Belyantseva IA, Noben-Trauth K, Cantos R, Chen A, Thakkar SI, Hoogstraten-Miller SL, Kachar B, Wu DK, Green ED: Targeted disruption of mouse Pds provides insight about the inner-ear defects encountered in Pendred syndrome. Hum Mol Genet 2001;10:153–161.
  8. Fugazzola L, Mannavola D, Cerutti N, Maghnie M, Pagella F, Bianchi P, Weber G, Persani L, Beck-Peccoz P: Molecular analysis of the Pendred’s syndrome gene and magnetic resonance imaging studies of the inner ear are essential for the diagnosis of true Pendred’s syndrome. J Clin Endocrinol Metab 2000;85:2469–2475.
  9. Gonzalez Trevino O, Karamanoglu Arseven O, Ceballos CJ, Vives VI, Ramirez RC, Gomez VV, Medeiros-Neto G, Kopp P: Clinical and molecular analysis of three Mexican families with Pendred’s syndrome. Eur J Endocrinol 2001;144:585–593.
  10. Griffith AJ, Telian SA, Downs C, Gorski JL, Gebarski SS, Lalwani AK, Sheldon S: Familial Mondini dysplasia. Laryngoscope 1998;108:1368–1373.
  11. Hulander M, Kiernan AE, Blomqvist SR, Carlsson P, Samuelsson EJ, Johansson BR, Steel KP, Enerback S: Lack of pendrin expression leads to deafness and expansion of the endolymphatic compartment in inner ears of Foxi1 null mutant mice. Development 2003;130:2013–2025.
  12. Illum P: The Mondini type of cochlear malformation. A survey of the literature. Arch Otolaryngol Head Neck Surg 1972;96:305–311.
  13. Jackler RK, Luxford WM, House WF: Congenital malformations of the inner ear: A classification based on embryogenesis. Laryngoscope 1987;97(suppl 40):2–14.

    External Resources

  14. Li XC, Everett LA, Lalwani AK, Desmukh D, Friedman TB, Green ED, Wilcox ER: A mutation in PDS causes non-syndromic recessive deafness. Nat Genet 1998;18:215–217.
  15. Mafong DD, Shin EJ, Lalwani AK: Use of laboratory evaluation and radiologic imaging in the diagnostic evaluation of children with sensorineural hearing loss. Laryngoscope 2002;112:1–7.
  16. McClay JE, Tandy R, Grundfast K, Choi S, Vezina G, Zalzal G, Willner A: Major and minor temporal bone abnormalities in children with and without congenital sensorineural hearing loss. Arch Otolaryngol Head Neck Surg 2002;128:664–671.
  17. Park HJ, Shaukat S, Liu XZ, Hahn SH, Naz S, Ghosh M, Kim HN, Moon SK, Abe S, Tukamoto K, Riazuddin S, Kabra M, Erdenetungalag R, Radnaabazar J, Khan S, Pandya A, Usami SI, Nance WE, Wilcox ER, Riazuddin S, Griffith AJ: Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: Global implications for the epidemiology of deafness. J Med Genet 2003;40:241–248.

    External Resources

  18. Phelps PD: Mondini and pseudo-Mondini. Clin Otolaryngol 1990;15:99–101.
  19. Purcell D, Johnson J, Fischbein N, Lalwani AK: Establishment of normative cochlear and vestibular measurements to aid in the diagnosis of inner ear malformations. Otolaryngol Head Neck Surg 2003;128:78–87.
  20. Pyle GM: Embryological development and large vestibular aqueduct syndrome. Laryngoscope 2000;110:1837–1842.
  21. Royaux IE, Suzuki K, Mori A, Katoh R, Everett LA, Kohn LD, Green ED: Pendrin, the protein encoded by the Pendred syndrome gene (PDS), is an apical porter of iodide in the thyroid and is regulated by thyroglobulin in FRTL-5 cells. Endocrinology 2000;141:839–845.
  22. Royaux IE, Belyantseva IA, Wu T, Kachar B, Everett LA, Marcus DC, Green ED: Localization and functional studies of pendrin in the mouse inner ear provide insight about the etiology of deafness in pendred syndrome. J Assoc Res Otolaryngol 2003;4:394–404.
  23. Scott DA, Wang R, Kreman TM, Sheffield VC, Karniski LP: The Pendred syndrome gene encodes a chloride-iodide transport protein. Nat Genet 1999;21:440–443.
  24. Scott DA, Karniski LP: Human pendrin expressed in Xenopus laevis oocytes mediates chloride/formate exchange. Am J Physiol Cell Physiol 2000;278:C207–211.
  25. Sennaroglu L, Saatci I: A new classification for cochleovestibular malformations. Laryngoscope 2002;112:2230–2241.
  26. 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;11:916–922.
  27. Usami S, Abe S, Weston MD, Shinkawa H, Van Camp G, Kimberling WJ: Non-syndromic hearing loss associated with enlarged vestibular aqueduct is caused by PDS mutation. Hum Genet 1999;104:188–192.
  28. Wu CC, Chen YS, Chen PJ, Hsu CJ: Common clinical features of children with enlarged vestibular aqueduct and Mondini dysplasia. Laryngoscope 2005;115:132–137.
  29. Yoshida A, Hisatome I, Taniguchi S, Sasaki N, Yamamoto Y, Miake J, Fukui H, Shimizu H, Okamura T, Okura T, Igawa O, Shigemasa C, Green ED, Kohn LD, Suzuki K: Mechanism of iodide/chloride exchange by Pendrin. Endocrinology 2004;145:4301–4308.
  30. Zheng Y, Schachern PA, Cureoglu S, Mutlu C, Dijalilian H, Paparella MM: The shortened cochlea: Its classification and histopathologic features. Int J Pediatr Otorhinolaryngol 2002;63:29–39.


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