Cargando…
Pathogenic substitution of IVS15 + 5G > A in SLC26A4 in patients of Okinawa Islands with enlarged vestibular aqueduct syndrome or Pendred syndrome
BACKGROUND: Pendred syndrome (PS) and nonsyndromic hearing loss associated with enlarged vestibular aqueduct (EVA) are caused by SLC26A4 mutations. The Okinawa Islands are the southwestern-most islands of the Japanese archipelago. And ancestral differences have been reported between people from Okin...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664218/ https://www.ncbi.nlm.nih.gov/pubmed/23705809 http://dx.doi.org/10.1186/1471-2350-14-56 |
_version_ | 1782271075762044928 |
---|---|
author | Ganaha, Akira Kaname, Tadashi Yanagi, Kumiko Naritomi, Kenji Tono, Tetsuya Usami, Shin-ichi Suzuki, Mikio |
author_facet | Ganaha, Akira Kaname, Tadashi Yanagi, Kumiko Naritomi, Kenji Tono, Tetsuya Usami, Shin-ichi Suzuki, Mikio |
author_sort | Ganaha, Akira |
collection | PubMed |
description | BACKGROUND: Pendred syndrome (PS) and nonsyndromic hearing loss associated with enlarged vestibular aqueduct (EVA) are caused by SLC26A4 mutations. The Okinawa Islands are the southwestern-most islands of the Japanese archipelago. And ancestral differences have been reported between people from Okinawa Island and those from the main islands of Japan. To confirm the ethnic variation of the spectrum of SLC26A4 mutations, we investigated the frequencies of SLC26A4 mutations and clinical manifestations of patients with EVA or PS living in the Okinawa Islands. METHODS: We examined 22 patients with EVA or PS from 21 unrelated families in Okinawa Islands. The patient’s clinical history, findings of physical and otoscopic examinations, hearing test, and computed tomography (CT) scan of the temporal bones were recorded. To detect mutations, all 21 exons and the exon–intron junctions of SLC26A4 were sequenced for all subjects. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) for SLC26A4 and calculations using the comparative CT (2(−ΔΔCT)) method were used to determine the pathogenicity associated with gene substitutions. RESULTS: SLC26A4 mutations were identified in 21 of the 22 patients. We found a compound heterozygous mutation for IVS15 + 5G > A/H723R in nine patients (41%), a homozygous substitution of IVS15 + 5G > A in six patients (27%), and homozygous mutation for H723R in five patients (23%). The most prevalent types of SLC26A4 alleles were IVS15 + 5G > A and H723R, which both accounted for 15/22 (68%) of the patients. There were no significant correlations between the types of SLC26A4 mutation and clinical manifestations. Based on qRT-PCR results, expression of SLC26A4 was not identified in patients with the homozygous substitution of IVS15 + 5G > A. CONCLUSIONS: The substitution of IVS15 + 5G > A in SLC26A4 was the most common mutation in uniquely found in patients with PS and EVA in Okinawa Islands. This suggested that the spectrum of SLC26A4 mutation differed from main islands of Japan and other East Asian countries. The substitution of IVS15 + 5G > A leads to a loss of SLC26A expression and results in a phenotype of PS and EVA. |
format | Online Article Text |
id | pubmed-3664218 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-36642182013-05-27 Pathogenic substitution of IVS15 + 5G > A in SLC26A4 in patients of Okinawa Islands with enlarged vestibular aqueduct syndrome or Pendred syndrome Ganaha, Akira Kaname, Tadashi Yanagi, Kumiko Naritomi, Kenji Tono, Tetsuya Usami, Shin-ichi Suzuki, Mikio BMC Med Genet Research Article BACKGROUND: Pendred syndrome (PS) and nonsyndromic hearing loss associated with enlarged vestibular aqueduct (EVA) are caused by SLC26A4 mutations. The Okinawa Islands are the southwestern-most islands of the Japanese archipelago. And ancestral differences have been reported between people from Okinawa Island and those from the main islands of Japan. To confirm the ethnic variation of the spectrum of SLC26A4 mutations, we investigated the frequencies of SLC26A4 mutations and clinical manifestations of patients with EVA or PS living in the Okinawa Islands. METHODS: We examined 22 patients with EVA or PS from 21 unrelated families in Okinawa Islands. The patient’s clinical history, findings of physical and otoscopic examinations, hearing test, and computed tomography (CT) scan of the temporal bones were recorded. To detect mutations, all 21 exons and the exon–intron junctions of SLC26A4 were sequenced for all subjects. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) for SLC26A4 and calculations using the comparative CT (2(−ΔΔCT)) method were used to determine the pathogenicity associated with gene substitutions. RESULTS: SLC26A4 mutations were identified in 21 of the 22 patients. We found a compound heterozygous mutation for IVS15 + 5G > A/H723R in nine patients (41%), a homozygous substitution of IVS15 + 5G > A in six patients (27%), and homozygous mutation for H723R in five patients (23%). The most prevalent types of SLC26A4 alleles were IVS15 + 5G > A and H723R, which both accounted for 15/22 (68%) of the patients. There were no significant correlations between the types of SLC26A4 mutation and clinical manifestations. Based on qRT-PCR results, expression of SLC26A4 was not identified in patients with the homozygous substitution of IVS15 + 5G > A. CONCLUSIONS: The substitution of IVS15 + 5G > A in SLC26A4 was the most common mutation in uniquely found in patients with PS and EVA in Okinawa Islands. This suggested that the spectrum of SLC26A4 mutation differed from main islands of Japan and other East Asian countries. The substitution of IVS15 + 5G > A leads to a loss of SLC26A expression and results in a phenotype of PS and EVA. BioMed Central 2013-05-24 /pmc/articles/PMC3664218/ /pubmed/23705809 http://dx.doi.org/10.1186/1471-2350-14-56 Text en Copyright © 2013 Ganaha et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Ganaha, Akira Kaname, Tadashi Yanagi, Kumiko Naritomi, Kenji Tono, Tetsuya Usami, Shin-ichi Suzuki, Mikio Pathogenic substitution of IVS15 + 5G > A in SLC26A4 in patients of Okinawa Islands with enlarged vestibular aqueduct syndrome or Pendred syndrome |
title | Pathogenic substitution of IVS15 + 5G > A in SLC26A4 in patients of Okinawa Islands with enlarged vestibular aqueduct syndrome or Pendred syndrome |
title_full | Pathogenic substitution of IVS15 + 5G > A in SLC26A4 in patients of Okinawa Islands with enlarged vestibular aqueduct syndrome or Pendred syndrome |
title_fullStr | Pathogenic substitution of IVS15 + 5G > A in SLC26A4 in patients of Okinawa Islands with enlarged vestibular aqueduct syndrome or Pendred syndrome |
title_full_unstemmed | Pathogenic substitution of IVS15 + 5G > A in SLC26A4 in patients of Okinawa Islands with enlarged vestibular aqueduct syndrome or Pendred syndrome |
title_short | Pathogenic substitution of IVS15 + 5G > A in SLC26A4 in patients of Okinawa Islands with enlarged vestibular aqueduct syndrome or Pendred syndrome |
title_sort | pathogenic substitution of ivs15 + 5g > a in slc26a4 in patients of okinawa islands with enlarged vestibular aqueduct syndrome or pendred syndrome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664218/ https://www.ncbi.nlm.nih.gov/pubmed/23705809 http://dx.doi.org/10.1186/1471-2350-14-56 |
work_keys_str_mv | AT ganahaakira pathogenicsubstitutionofivs155gainslc26a4inpatientsofokinawaislandswithenlargedvestibularaqueductsyndromeorpendredsyndrome AT kanametadashi pathogenicsubstitutionofivs155gainslc26a4inpatientsofokinawaislandswithenlargedvestibularaqueductsyndromeorpendredsyndrome AT yanagikumiko pathogenicsubstitutionofivs155gainslc26a4inpatientsofokinawaislandswithenlargedvestibularaqueductsyndromeorpendredsyndrome AT naritomikenji pathogenicsubstitutionofivs155gainslc26a4inpatientsofokinawaislandswithenlargedvestibularaqueductsyndromeorpendredsyndrome AT tonotetsuya pathogenicsubstitutionofivs155gainslc26a4inpatientsofokinawaislandswithenlargedvestibularaqueductsyndromeorpendredsyndrome AT usamishinichi pathogenicsubstitutionofivs155gainslc26a4inpatientsofokinawaislandswithenlargedvestibularaqueductsyndromeorpendredsyndrome AT suzukimikio pathogenicsubstitutionofivs155gainslc26a4inpatientsofokinawaislandswithenlargedvestibularaqueductsyndromeorpendredsyndrome |