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Mutational Spectrum and Clinical Features of Patients with LOXHD1 Variants Identified in an 8074 Hearing Loss Patient Cohort

Variants of the LOXHD1 gene, which are expressed in hair cells of the cochlea and vestibule, have been reported to cause a progressive form of autosomal recessive non-syndromic hereditary hearing loss, DFNB77. In this study, genetic screening was conducted on 8074 Japanese hearing loss patients util...

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Autores principales: Maekawa, Karuna, Nishio, Shin-ya, Abe, Satoko, Goto, Shin-ichi, Honkura, Yohei, Iwasaki, Satoshi, Kanda, Yukihiko, Kobayashi, Yumiko, Oka, Shin-ichiro, Okami, Mayuri, Oshikawa, Chie, Sakuma, Naoko, Sano, Hajime, Shirakura, Masayuki, Uehara, Natsumi, Usami, Shin-ichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826470/
https://www.ncbi.nlm.nih.gov/pubmed/31547530
http://dx.doi.org/10.3390/genes10100735
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author Maekawa, Karuna
Nishio, Shin-ya
Abe, Satoko
Goto, Shin-ichi
Honkura, Yohei
Iwasaki, Satoshi
Kanda, Yukihiko
Kobayashi, Yumiko
Oka, Shin-ichiro
Okami, Mayuri
Oshikawa, Chie
Sakuma, Naoko
Sano, Hajime
Shirakura, Masayuki
Uehara, Natsumi
Usami, Shin-ichi
author_facet Maekawa, Karuna
Nishio, Shin-ya
Abe, Satoko
Goto, Shin-ichi
Honkura, Yohei
Iwasaki, Satoshi
Kanda, Yukihiko
Kobayashi, Yumiko
Oka, Shin-ichiro
Okami, Mayuri
Oshikawa, Chie
Sakuma, Naoko
Sano, Hajime
Shirakura, Masayuki
Uehara, Natsumi
Usami, Shin-ichi
author_sort Maekawa, Karuna
collection PubMed
description Variants of the LOXHD1 gene, which are expressed in hair cells of the cochlea and vestibule, have been reported to cause a progressive form of autosomal recessive non-syndromic hereditary hearing loss, DFNB77. In this study, genetic screening was conducted on 8074 Japanese hearing loss patients utilizing massively parallel DNA sequencing to identify individuals with LOXHD1 variants and to assess their phenotypes. A total of 28 affected individuals and 21 LOXHD1 variants were identified, among which 13 were novel variants. A recurrent variant c.4212 + 1G > A, only reported in Japanese patients, was detected in 18 individuals. Haplotype analysis implied that this variation occurred in a mutational hot spot, and that multiple ancestors of Japanese population had this variation. Patients with LOXHD1 variations mostly showed early onset hearing loss and presented different progression rates. We speculated that the varying severities and progression rates of hearing loss are the result of environmental and/or other genetic factors. No accompanying symptoms, including vestibular dysfunction, with hearing loss were detected in this study. Few studies have reported the clinical features of LOXHD1-gene associated hearing loss, and this study is by far the largest study focused on the evaluation of this gene.
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spelling pubmed-68264702019-11-18 Mutational Spectrum and Clinical Features of Patients with LOXHD1 Variants Identified in an 8074 Hearing Loss Patient Cohort Maekawa, Karuna Nishio, Shin-ya Abe, Satoko Goto, Shin-ichi Honkura, Yohei Iwasaki, Satoshi Kanda, Yukihiko Kobayashi, Yumiko Oka, Shin-ichiro Okami, Mayuri Oshikawa, Chie Sakuma, Naoko Sano, Hajime Shirakura, Masayuki Uehara, Natsumi Usami, Shin-ichi Genes (Basel) Article Variants of the LOXHD1 gene, which are expressed in hair cells of the cochlea and vestibule, have been reported to cause a progressive form of autosomal recessive non-syndromic hereditary hearing loss, DFNB77. In this study, genetic screening was conducted on 8074 Japanese hearing loss patients utilizing massively parallel DNA sequencing to identify individuals with LOXHD1 variants and to assess their phenotypes. A total of 28 affected individuals and 21 LOXHD1 variants were identified, among which 13 were novel variants. A recurrent variant c.4212 + 1G > A, only reported in Japanese patients, was detected in 18 individuals. Haplotype analysis implied that this variation occurred in a mutational hot spot, and that multiple ancestors of Japanese population had this variation. Patients with LOXHD1 variations mostly showed early onset hearing loss and presented different progression rates. We speculated that the varying severities and progression rates of hearing loss are the result of environmental and/or other genetic factors. No accompanying symptoms, including vestibular dysfunction, with hearing loss were detected in this study. Few studies have reported the clinical features of LOXHD1-gene associated hearing loss, and this study is by far the largest study focused on the evaluation of this gene. MDPI 2019-09-23 /pmc/articles/PMC6826470/ /pubmed/31547530 http://dx.doi.org/10.3390/genes10100735 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Maekawa, Karuna
Nishio, Shin-ya
Abe, Satoko
Goto, Shin-ichi
Honkura, Yohei
Iwasaki, Satoshi
Kanda, Yukihiko
Kobayashi, Yumiko
Oka, Shin-ichiro
Okami, Mayuri
Oshikawa, Chie
Sakuma, Naoko
Sano, Hajime
Shirakura, Masayuki
Uehara, Natsumi
Usami, Shin-ichi
Mutational Spectrum and Clinical Features of Patients with LOXHD1 Variants Identified in an 8074 Hearing Loss Patient Cohort
title Mutational Spectrum and Clinical Features of Patients with LOXHD1 Variants Identified in an 8074 Hearing Loss Patient Cohort
title_full Mutational Spectrum and Clinical Features of Patients with LOXHD1 Variants Identified in an 8074 Hearing Loss Patient Cohort
title_fullStr Mutational Spectrum and Clinical Features of Patients with LOXHD1 Variants Identified in an 8074 Hearing Loss Patient Cohort
title_full_unstemmed Mutational Spectrum and Clinical Features of Patients with LOXHD1 Variants Identified in an 8074 Hearing Loss Patient Cohort
title_short Mutational Spectrum and Clinical Features of Patients with LOXHD1 Variants Identified in an 8074 Hearing Loss Patient Cohort
title_sort mutational spectrum and clinical features of patients with loxhd1 variants identified in an 8074 hearing loss patient cohort
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826470/
https://www.ncbi.nlm.nih.gov/pubmed/31547530
http://dx.doi.org/10.3390/genes10100735
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