Correlation between genotype and phenotype in patients with bi-allelic SLC26A4 mutations

H. J. Lee, J. Jung, J. W. Shin, M. H. Song, S. H. Kim, J. H. Lee, K. A. Lee, S. Shin, U. K. Kim, J. Bok, K. Y. Lee, J. Y. Choi, H. J. Park

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Mutation of SLC26A4 is the most common cause of prelingual hearing loss in East Asia. Patients with SLC26A4 mutations have variable phenotypes ranging from non-syndromic hearing loss to Pendred syndrome. Here, we analyzed the correlation between genotype and various inner ear phenotypes and found a possible underlying mechanism. This study included 111 patients with bi-allelic SLC26A4 mutations who had bilateral enlarged vestibular aqueduct (EVA) and hearing loss. p.H723R (61%), c.919-2A>G (24%), and p.T410M (4%) were the most common mutations in Korean patients with EVAs. Residual hearing in patients with c.919-2A>G or p.T410M mutations was better than that of patients with p.H723R homozygous mutations. Interestingly, quantitative polymerase chain reaction showed normal pendrin transcript (6-17% of normal levels) was produced from patients with c.919-2A>G homozygous mutations. Surface expression ratio of pendrin and residual anion exchange activity were higher in cells transfected with p.T410M in comparison to cells transfected with p.H723R. These results suggest that there is a correlation between degree of residual hearing and the SLC26A4 genotype commonly found in the East Asian population.

Original languageEnglish
Pages (from-to)270-275
Number of pages6
JournalClinical Genetics
Volume86
Issue number3
DOIs
Publication statusPublished - 2014 Sep

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Genetic Association Studies
Mutation
Hearing Loss
Hearing
Extravehicular Activity
Genotype
Phenotype
Far East
Inner Ear
Anions
Polymerase Chain Reaction
Population

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Lee, H. J., Jung, J., Shin, J. W., Song, M. H., Kim, S. H., Lee, J. H., ... Park, H. J. (2014). Correlation between genotype and phenotype in patients with bi-allelic SLC26A4 mutations. Clinical Genetics, 86(3), 270-275. https://doi.org/10.1111/cge.12273
Lee, H. J. ; Jung, J. ; Shin, J. W. ; Song, M. H. ; Kim, S. H. ; Lee, J. H. ; Lee, K. A. ; Shin, S. ; Kim, U. K. ; Bok, J. ; Lee, K. Y. ; Choi, J. Y. ; Park, H. J. / Correlation between genotype and phenotype in patients with bi-allelic SLC26A4 mutations. In: Clinical Genetics. 2014 ; Vol. 86, No. 3. pp. 270-275.
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abstract = "Mutation of SLC26A4 is the most common cause of prelingual hearing loss in East Asia. Patients with SLC26A4 mutations have variable phenotypes ranging from non-syndromic hearing loss to Pendred syndrome. Here, we analyzed the correlation between genotype and various inner ear phenotypes and found a possible underlying mechanism. This study included 111 patients with bi-allelic SLC26A4 mutations who had bilateral enlarged vestibular aqueduct (EVA) and hearing loss. p.H723R (61{\%}), c.919-2A>G (24{\%}), and p.T410M (4{\%}) were the most common mutations in Korean patients with EVAs. Residual hearing in patients with c.919-2A>G or p.T410M mutations was better than that of patients with p.H723R homozygous mutations. Interestingly, quantitative polymerase chain reaction showed normal pendrin transcript (6-17{\%} of normal levels) was produced from patients with c.919-2A>G homozygous mutations. Surface expression ratio of pendrin and residual anion exchange activity were higher in cells transfected with p.T410M in comparison to cells transfected with p.H723R. These results suggest that there is a correlation between degree of residual hearing and the SLC26A4 genotype commonly found in the East Asian population.",
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Lee, HJ, Jung, J, Shin, JW, Song, MH, Kim, SH, Lee, JH, Lee, KA, Shin, S, Kim, UK, Bok, J, Lee, KY, Choi, JY & Park, HJ 2014, 'Correlation between genotype and phenotype in patients with bi-allelic SLC26A4 mutations', Clinical Genetics, vol. 86, no. 3, pp. 270-275. https://doi.org/10.1111/cge.12273

Correlation between genotype and phenotype in patients with bi-allelic SLC26A4 mutations. / Lee, H. J.; Jung, J.; Shin, J. W.; Song, M. H.; Kim, S. H.; Lee, J. H.; Lee, K. A.; Shin, S.; Kim, U. K.; Bok, J.; Lee, K. Y.; Choi, J. Y.; Park, H. J.

In: Clinical Genetics, Vol. 86, No. 3, 09.2014, p. 270-275.

Research output: Contribution to journalArticle

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AU - Lee, H. J.

AU - Jung, J.

AU - Shin, J. W.

AU - Song, M. H.

AU - Kim, S. H.

AU - Lee, J. H.

AU - Lee, K. A.

AU - Shin, S.

AU - Kim, U. K.

AU - Bok, J.

AU - Lee, K. Y.

AU - Choi, J. Y.

AU - Park, H. J.

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N2 - Mutation of SLC26A4 is the most common cause of prelingual hearing loss in East Asia. Patients with SLC26A4 mutations have variable phenotypes ranging from non-syndromic hearing loss to Pendred syndrome. Here, we analyzed the correlation between genotype and various inner ear phenotypes and found a possible underlying mechanism. This study included 111 patients with bi-allelic SLC26A4 mutations who had bilateral enlarged vestibular aqueduct (EVA) and hearing loss. p.H723R (61%), c.919-2A>G (24%), and p.T410M (4%) were the most common mutations in Korean patients with EVAs. Residual hearing in patients with c.919-2A>G or p.T410M mutations was better than that of patients with p.H723R homozygous mutations. Interestingly, quantitative polymerase chain reaction showed normal pendrin transcript (6-17% of normal levels) was produced from patients with c.919-2A>G homozygous mutations. Surface expression ratio of pendrin and residual anion exchange activity were higher in cells transfected with p.T410M in comparison to cells transfected with p.H723R. These results suggest that there is a correlation between degree of residual hearing and the SLC26A4 genotype commonly found in the East Asian population.

AB - Mutation of SLC26A4 is the most common cause of prelingual hearing loss in East Asia. Patients with SLC26A4 mutations have variable phenotypes ranging from non-syndromic hearing loss to Pendred syndrome. Here, we analyzed the correlation between genotype and various inner ear phenotypes and found a possible underlying mechanism. This study included 111 patients with bi-allelic SLC26A4 mutations who had bilateral enlarged vestibular aqueduct (EVA) and hearing loss. p.H723R (61%), c.919-2A>G (24%), and p.T410M (4%) were the most common mutations in Korean patients with EVAs. Residual hearing in patients with c.919-2A>G or p.T410M mutations was better than that of patients with p.H723R homozygous mutations. Interestingly, quantitative polymerase chain reaction showed normal pendrin transcript (6-17% of normal levels) was produced from patients with c.919-2A>G homozygous mutations. Surface expression ratio of pendrin and residual anion exchange activity were higher in cells transfected with p.T410M in comparison to cells transfected with p.H723R. These results suggest that there is a correlation between degree of residual hearing and the SLC26A4 genotype commonly found in the East Asian population.

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