Abstract
Pendred syndrome is an autosomal recessive inherited disorder characterized by a combination of sensorineural hearing impairment and euthyroid goiter; its clinical manifestation in children is hardly distinguishable from nonsyndromic hearing loss. Pendred syndrome is one of the most frequent types of syndromic hearing loss. Hearing impairment is accompanied by abnormal development of the bony labyrinth—enlarged vestibular aqueduct (EVA) and occasionally combined with Mondini dysplasia. Mutations in the SLC26A4 gene, which encodes the pendrin protein, are responsible for both Pendred syndrome and for allelic disorder (nonsyndromic enlarged vestibular aqueduct). The present study for the first time conducted molecular genetic analysis in 20 Russian patients with Pendred syndrome, EVA and/or Mondini dysplasia. As a result, six pathogenic mutations in the SLC26A4 gene were revealed in four patients. The mutation c.222G>T (p.Trp74Cys) was detected for the first time. Mutations were found in patients with Pendred syndrome and nonsyndromic EVA with or without Mondini dysplasia. Mutations were not detected in patients with isolated Mondini dysplasia. One proband with clinical diagnosis Pendred syndrome was homozygous for the c.35delG mutation in the GJB2 gene. The absence of frequent mutations, including well-known ones or “hot” exons in the SLC26A4 gene, was reported. Therefore, the optimal method to search for mutations in the SLC26A4 gene in Russian patients is Sanger sequencing of all exons and exon-intron boundaries in the SLC26A4 gene.
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Bliznetz, E.A., Galkina, V.A., Matyushchenko, G.N., et al., Changes in the connexin 26 gene (GJB2) in Russian patients with hearing loss: results of long term molecular diagnostics of hereditary nonsyndromic hearing loss, Russ. J. Genet., 2012, vol. 48, no. 1, pp. 101–112.
Markova, T.G., Polyakov, A.V., and Kunel’skaya, N.L., Clinic of hearing disorders due to changes in the connexin 26 gene, Vestn. Otorinolaringol., 2008, vol. 1, no. 2, pp. 4–9.
Tavartkiladze, G.A., Polyakov, A.V., Markova, T.G., et al., Genetic screening for hearing disorders in newborn infants in combination with audiological screening, Vestn. Otorinolaringol., 2010, vol. 3, no. 15, pp. 15–18.
Van Camp, G., Willems, P.J., and Smith, R.J., Nonsyndromic hearing impairment: unparalleled heterogeneity, Am. J. Hum. Genet., 1997, vol. 60, no. 4, pp. 758–764.
Toriello, H.V., Cohen, M.M., Gorlin, R.J., et al., Hereditary Hearing Loss and Its Syndromes, Oxford, 2004.
Ito, T., Choi, B.Y., King, K.A., et al., SLC26A4 genotypes and phenotypes associated with enlargement of the vestibular aqueduct, Cell Physiol. Biochem., 2011, vol. 28, pp. 545–552. doi 10.1159/000335119
Stinckens, C., Huygen, P.L., Joosten, F.B., et al., Fluctuant, progressive hearing loss associated with Menière like vertigo in three patients with the Pendred syndrome, Int. J. Pediatr. Otorhinolaryngol., 2001, vol. 61, pp. 207–215.
Luxon, L.M., Cohen, M., Coffey, R.A., et al., Neurootological findings in Pendred syndrome, Int. J. Audiol., 2003, vol. 42, pp. 82–88.
Fugazzola, L., Mannavola, D., Cerutti, N., et al., 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, vol. 85, pp. 2469–2475.
Bizhanova, A. and Kopp, P., Genetics and phenomics of Pendred syndrome, Mol. Cell. Endocrinol., 2010, vol. 322. nos. 1–2, pp. 83–90.
Wangemann, P., Nakaya, K., Wu, T., 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, vol. 292, pp. 1345–1353. doi 10.1152/ajprenal.00487.2006
Pera, A., Dossena, S., Rodighiero, S., et al., Functional assessment of allelic variants in the SLC26A4 gene involved in Pendred syndrome and nonsyndromic EVA, Proc. Natl. Acad. Sci. U.S.A., 2008, vol. 105, no. 47, pp. 18608–18613. doi 10.1073/pnas.0805831105
Coyle, B., Reardon, W., Herbrick, J.A., et al., Molecular analysis of the PDS gene in Pendred syndrome, Hum. Mol. Genet., 1998, vol. 7, pp. 1105–1112.
Tsukamoto, K., Suzuki, H., Harada, D., et al., 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, vol. 11, pp. 916–922.
Wu, C.C., Yeh, T.H., Chen, P.J., and Hsu, C.J., Prevalent SLC26A4 mutations in patients with enlarged vestibular aqueduct and/or Mondini dysplasia: a unique spectrum of mutations in Taiwan, including a frequent founder mutation, Laryngoscope, 2005, vol. 115, pp. 1060–1064.
Pera, A., Villamar, M., and Vinuela, A., A mutational analysis of the SLC26A4 gene in Spanish hearingimpaired families provides new insights into the genetic 138 RUSSIAN JOURNAL OFGENETICS Vol. 53 No. 1 2017 MIRONOVICH et al. causes of Pendred syndrome and DFNB4 hearing loss, Eur. J. Hum. Genet., 2008, vol. 16, pp. 888–896. doi 10.1038/ejhg.2008.30
Pryor, S.P., Madeo, A.C., Reynolds, J.C., et al., SLC26A4/PDS genotype-phenotype correlation in hearing loss with enlargement of the vestibular aqueduct (EVA): evidence that Pendred syndrome and nonsyndromic EVA are distinct clinical and genetic entities, J. Med. Genet., 2005, vol. 42, no. 2, pp. 159–165.
Azaiez, H., Yang, T., Prasad, S., et al., Genotype—phenotype correlations for SLC26A4-related deafness, Hum. Genet., 2007, vol. 122, pp. 451–457.
Borck, G., Napiontek, U., Pfarr, N., et al., Deafness and Goiter: Pendred Syndrome, Dtsch. Arztebl., 2006, vol. 103, no. 46, pp. 3108–3114.
Lobov, S.L., Structural features of pendrina (SLC26A4) and prestin (SLC26A5) genes in patients with hereditary non-syndromic sensorineural deafness Extended Abstract of Cand. Sci. Dissertation, Inst. Biokhim. Genet. Ural. Nauch. Tsentr Ross. Akad. Nauk, Moscow, 2013.
Huang, S., Han, D., Wang, G., et al., Sensorineural hearing loss caused by mutations in two alleles of both GJB2 and SLC26A4 genes, Int. J. Pediatr. Otorhinolaryngol., 2013, vol. 77, no. 3, pp. 379–383. doi 10.1016/j.ijporl.2012.11.031
Lu, Y.J., Yao, J., Wei, Q.J., et al., Diagnostic value of SLC26A4 mutation status in hereditary hearing loss with EVA: a PRISMA-Compliant Meta-Analysis, Medicine (Baltimore), 2015, vol. 94, no. 50. p. 2248. doi 10.1097/MD.0000000000002248
Campbell, C.I., Cucci, R.A., Prasad, S., et al., Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations and possible genotype—phenotype correlations, Hum. Mutat., 2001, vol. 17, no. 5, pp. 403–411.
Walsh, T.I., Abu Rayan, A., Abu Sa’ed, J., et al., Genomic analysis of a heterodeneous Mendelian phenotype: multiple novel alleles for inherited hearing loss in the Palestinian populiation, Hum. Genomics, 2006, vol. 2, no. 4, pp. 203–211.
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Original Russian Text © O.L. Mironovich, E.A. Bliznetz, T.G. Markova, E.N. Geptner, M.R. Lalayants, E.I. Zelikovich, G.A. Tavartkiladze, A.V. Polyakov, 2017, published in Genetika, 2017, Vol. 53, No. 1, pp. 88–99.
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Mironovich, O.L., Bliznetz, E.A., Markova, T.G. et al. Results of molecular genetic testing in Russian patients with Pendred syndrome and allelic disorders. Russ J Genet 53, 128–138 (2017). https://doi.org/10.1134/S1022795416120085
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DOI: https://doi.org/10.1134/S1022795416120085