Prevalence of TECTA mutation in patients with mid-frequency sensorineural hearing loss

Nobuko Yamamoto, Hideki Mutai, Kazunori Namba, Noriko Morita, Shin Masuda, Yasuyuki Nishi, Atsuko Nakano, Sawako Masuda, Masato Fujioka, Kimitaka Kaga, Kaoru Ogawa, Tatsuo Matsunaga

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: To date, 102 genes have been reported as responsible for non-syndromic hearing loss, some of which are associated with specific audiogram features. Four genes have been reported as causative for mid-frequency sensorineural hearing loss (MFSNHL), among which TECTA is the most frequently reported; however, the prevalence of TECTA mutations is unknown. To elucidate the prevalence of TECTA mutation in MFSNHL and clarify genotype-phenotype correlations, we analyzed the genetic and clinical features of patients with MFSNHL. Methods: Subjects with bilateral non-syndromic hearing loss were prescreened for GJB2 and m.1555A > G and m.3243A > G mitochondrial DNA mutations, and patients with inner ear malformations were excluded. We selected MFSNHL patients whose audiograms met the U-shaped criterion proposed by the GENDEAF study group, along with those with shallow U-shaped audiograms, for TECTA analysis. All TECTA exons were analyzed by Sanger sequencing. Novel missense variants were classified as possibly pathogenic, non-pathogenic, and variants of uncertain significance, based on genetic data. To evaluate novel possibly pathogenic variants, we predicted changes in protein structure by molecular modeling. Results: Pathogenic and possibly pathogenic variants of TECTA were found in 4 (6.0%) of 67 patients with MFSNHL. In patients with U-shaped audiograms, none (0%) of 21 had pathogenic or possibly pathogenic variants. In patients with shallow U-shaped audiograms, four (8.7%) of 46 had pathogenic or possibly pathogenic variants. Two novel possibly pathogenic variants were identified and two previously reported mutations were considered as variant of unknown significance. The clinical features of patients with pathogenic and possibly pathogenic variants were consistent with those in previous studies. Pathogenic or possibly pathogenic variants were identified in 3 of 23 families (13.0%) which have the family histories compatible with autosomal dominant and 1 of 44 families (2.3%) which have the family histories compatible with sporadic or autosomal recessive. Conclusions: TECTA mutations were identified in 6.0% of MFSNHL. These mutations were more frequent in patients with shallow U-shaped audiograms than those with U-shaped audiograms, and in families which have the family histories compatible with autosomal dominant than those with the family histories compatible with sporadic or autosomal recessive.

Original languageEnglish
Article number157
JournalOrphanet Journal of Rare Diseases
Volume12
Issue number1
DOIs
Publication statusPublished - 2017 Sep 25

Fingerprint

Sensorineural Hearing Loss
Mutation
Hearing Loss
Genetic Association Studies
Inner Ear
Molecular Structure
Mitochondrial DNA
Genes
Exons

Keywords

  • DFNA8/12
  • DFNB21
  • Mid-frequency hearing loss
  • TECTA

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)
  • Pharmacology (medical)

Cite this

Yamamoto, N., Mutai, H., Namba, K., Morita, N., Masuda, S., Nishi, Y., ... Matsunaga, T. (2017). Prevalence of TECTA mutation in patients with mid-frequency sensorineural hearing loss. Orphanet Journal of Rare Diseases, 12(1), [157]. https://doi.org/10.1186/s13023-017-0708-z

Prevalence of TECTA mutation in patients with mid-frequency sensorineural hearing loss. / Yamamoto, Nobuko; Mutai, Hideki; Namba, Kazunori; Morita, Noriko; Masuda, Shin; Nishi, Yasuyuki; Nakano, Atsuko; Masuda, Sawako; Fujioka, Masato; Kaga, Kimitaka; Ogawa, Kaoru; Matsunaga, Tatsuo.

In: Orphanet Journal of Rare Diseases, Vol. 12, No. 1, 157, 25.09.2017.

Research output: Contribution to journalArticle

Yamamoto, N, Mutai, H, Namba, K, Morita, N, Masuda, S, Nishi, Y, Nakano, A, Masuda, S, Fujioka, M, Kaga, K, Ogawa, K & Matsunaga, T 2017, 'Prevalence of TECTA mutation in patients with mid-frequency sensorineural hearing loss', Orphanet Journal of Rare Diseases, vol. 12, no. 1, 157. https://doi.org/10.1186/s13023-017-0708-z
Yamamoto, Nobuko ; Mutai, Hideki ; Namba, Kazunori ; Morita, Noriko ; Masuda, Shin ; Nishi, Yasuyuki ; Nakano, Atsuko ; Masuda, Sawako ; Fujioka, Masato ; Kaga, Kimitaka ; Ogawa, Kaoru ; Matsunaga, Tatsuo. / Prevalence of TECTA mutation in patients with mid-frequency sensorineural hearing loss. In: Orphanet Journal of Rare Diseases. 2017 ; Vol. 12, No. 1.
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abstract = "Background: To date, 102 genes have been reported as responsible for non-syndromic hearing loss, some of which are associated with specific audiogram features. Four genes have been reported as causative for mid-frequency sensorineural hearing loss (MFSNHL), among which TECTA is the most frequently reported; however, the prevalence of TECTA mutations is unknown. To elucidate the prevalence of TECTA mutation in MFSNHL and clarify genotype-phenotype correlations, we analyzed the genetic and clinical features of patients with MFSNHL. Methods: Subjects with bilateral non-syndromic hearing loss were prescreened for GJB2 and m.1555A > G and m.3243A > G mitochondrial DNA mutations, and patients with inner ear malformations were excluded. We selected MFSNHL patients whose audiograms met the U-shaped criterion proposed by the GENDEAF study group, along with those with shallow U-shaped audiograms, for TECTA analysis. All TECTA exons were analyzed by Sanger sequencing. Novel missense variants were classified as possibly pathogenic, non-pathogenic, and variants of uncertain significance, based on genetic data. To evaluate novel possibly pathogenic variants, we predicted changes in protein structure by molecular modeling. Results: Pathogenic and possibly pathogenic variants of TECTA were found in 4 (6.0{\%}) of 67 patients with MFSNHL. In patients with U-shaped audiograms, none (0{\%}) of 21 had pathogenic or possibly pathogenic variants. In patients with shallow U-shaped audiograms, four (8.7{\%}) of 46 had pathogenic or possibly pathogenic variants. Two novel possibly pathogenic variants were identified and two previously reported mutations were considered as variant of unknown significance. The clinical features of patients with pathogenic and possibly pathogenic variants were consistent with those in previous studies. Pathogenic or possibly pathogenic variants were identified in 3 of 23 families (13.0{\%}) which have the family histories compatible with autosomal dominant and 1 of 44 families (2.3{\%}) which have the family histories compatible with sporadic or autosomal recessive. Conclusions: TECTA mutations were identified in 6.0{\%} of MFSNHL. These mutations were more frequent in patients with shallow U-shaped audiograms than those with U-shaped audiograms, and in families which have the family histories compatible with autosomal dominant than those with the family histories compatible with sporadic or autosomal recessive.",
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AU - Yamamoto, Nobuko

AU - Mutai, Hideki

AU - Namba, Kazunori

AU - Morita, Noriko

AU - Masuda, Shin

AU - Nishi, Yasuyuki

AU - Nakano, Atsuko

AU - Masuda, Sawako

AU - Fujioka, Masato

AU - Kaga, Kimitaka

AU - Ogawa, Kaoru

AU - Matsunaga, Tatsuo

PY - 2017/9/25

Y1 - 2017/9/25

N2 - Background: To date, 102 genes have been reported as responsible for non-syndromic hearing loss, some of which are associated with specific audiogram features. Four genes have been reported as causative for mid-frequency sensorineural hearing loss (MFSNHL), among which TECTA is the most frequently reported; however, the prevalence of TECTA mutations is unknown. To elucidate the prevalence of TECTA mutation in MFSNHL and clarify genotype-phenotype correlations, we analyzed the genetic and clinical features of patients with MFSNHL. Methods: Subjects with bilateral non-syndromic hearing loss were prescreened for GJB2 and m.1555A > G and m.3243A > G mitochondrial DNA mutations, and patients with inner ear malformations were excluded. We selected MFSNHL patients whose audiograms met the U-shaped criterion proposed by the GENDEAF study group, along with those with shallow U-shaped audiograms, for TECTA analysis. All TECTA exons were analyzed by Sanger sequencing. Novel missense variants were classified as possibly pathogenic, non-pathogenic, and variants of uncertain significance, based on genetic data. To evaluate novel possibly pathogenic variants, we predicted changes in protein structure by molecular modeling. Results: Pathogenic and possibly pathogenic variants of TECTA were found in 4 (6.0%) of 67 patients with MFSNHL. In patients with U-shaped audiograms, none (0%) of 21 had pathogenic or possibly pathogenic variants. In patients with shallow U-shaped audiograms, four (8.7%) of 46 had pathogenic or possibly pathogenic variants. Two novel possibly pathogenic variants were identified and two previously reported mutations were considered as variant of unknown significance. The clinical features of patients with pathogenic and possibly pathogenic variants were consistent with those in previous studies. Pathogenic or possibly pathogenic variants were identified in 3 of 23 families (13.0%) which have the family histories compatible with autosomal dominant and 1 of 44 families (2.3%) which have the family histories compatible with sporadic or autosomal recessive. Conclusions: TECTA mutations were identified in 6.0% of MFSNHL. These mutations were more frequent in patients with shallow U-shaped audiograms than those with U-shaped audiograms, and in families which have the family histories compatible with autosomal dominant than those with the family histories compatible with sporadic or autosomal recessive.

AB - Background: To date, 102 genes have been reported as responsible for non-syndromic hearing loss, some of which are associated with specific audiogram features. Four genes have been reported as causative for mid-frequency sensorineural hearing loss (MFSNHL), among which TECTA is the most frequently reported; however, the prevalence of TECTA mutations is unknown. To elucidate the prevalence of TECTA mutation in MFSNHL and clarify genotype-phenotype correlations, we analyzed the genetic and clinical features of patients with MFSNHL. Methods: Subjects with bilateral non-syndromic hearing loss were prescreened for GJB2 and m.1555A > G and m.3243A > G mitochondrial DNA mutations, and patients with inner ear malformations were excluded. We selected MFSNHL patients whose audiograms met the U-shaped criterion proposed by the GENDEAF study group, along with those with shallow U-shaped audiograms, for TECTA analysis. All TECTA exons were analyzed by Sanger sequencing. Novel missense variants were classified as possibly pathogenic, non-pathogenic, and variants of uncertain significance, based on genetic data. To evaluate novel possibly pathogenic variants, we predicted changes in protein structure by molecular modeling. Results: Pathogenic and possibly pathogenic variants of TECTA were found in 4 (6.0%) of 67 patients with MFSNHL. In patients with U-shaped audiograms, none (0%) of 21 had pathogenic or possibly pathogenic variants. In patients with shallow U-shaped audiograms, four (8.7%) of 46 had pathogenic or possibly pathogenic variants. Two novel possibly pathogenic variants were identified and two previously reported mutations were considered as variant of unknown significance. The clinical features of patients with pathogenic and possibly pathogenic variants were consistent with those in previous studies. Pathogenic or possibly pathogenic variants were identified in 3 of 23 families (13.0%) which have the family histories compatible with autosomal dominant and 1 of 44 families (2.3%) which have the family histories compatible with sporadic or autosomal recessive. Conclusions: TECTA mutations were identified in 6.0% of MFSNHL. These mutations were more frequent in patients with shallow U-shaped audiograms than those with U-shaped audiograms, and in families which have the family histories compatible with autosomal dominant than those with the family histories compatible with sporadic or autosomal recessive.

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