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...

Descripción completa

Detalles Bibliográficos
Autores principales: Ganaha, Akira, Kaname, Tadashi, Yanagi, Kumiko, Naritomi, Kenji, Tono, Tetsuya, Usami, Shin-ichi, Suzuki, Mikio
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