Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783465094969032704 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6826470 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT maekawakaruna mutationalspectrumandclinicalfeaturesofpatientswithloxhd1variantsidentifiedinan8074hearinglosspatientcohort AT nishioshinya mutationalspectrumandclinicalfeaturesofpatientswithloxhd1variantsidentifiedinan8074hearinglosspatientcohort AT abesatoko mutationalspectrumandclinicalfeaturesofpatientswithloxhd1variantsidentifiedinan8074hearinglosspatientcohort AT gotoshinichi mutationalspectrumandclinicalfeaturesofpatientswithloxhd1variantsidentifiedinan8074hearinglosspatientcohort AT honkurayohei mutationalspectrumandclinicalfeaturesofpatientswithloxhd1variantsidentifiedinan8074hearinglosspatientcohort AT iwasakisatoshi mutationalspectrumandclinicalfeaturesofpatientswithloxhd1variantsidentifiedinan8074hearinglosspatientcohort AT kandayukihiko mutationalspectrumandclinicalfeaturesofpatientswithloxhd1variantsidentifiedinan8074hearinglosspatientcohort AT kobayashiyumiko mutationalspectrumandclinicalfeaturesofpatientswithloxhd1variantsidentifiedinan8074hearinglosspatientcohort AT okashinichiro mutationalspectrumandclinicalfeaturesofpatientswithloxhd1variantsidentifiedinan8074hearinglosspatientcohort AT okamimayuri mutationalspectrumandclinicalfeaturesofpatientswithloxhd1variantsidentifiedinan8074hearinglosspatientcohort AT oshikawachie mutationalspectrumandclinicalfeaturesofpatientswithloxhd1variantsidentifiedinan8074hearinglosspatientcohort AT sakumanaoko mutationalspectrumandclinicalfeaturesofpatientswithloxhd1variantsidentifiedinan8074hearinglosspatientcohort AT sanohajime mutationalspectrumandclinicalfeaturesofpatientswithloxhd1variantsidentifiedinan8074hearinglosspatientcohort AT shirakuramasayuki mutationalspectrumandclinicalfeaturesofpatientswithloxhd1variantsidentifiedinan8074hearinglosspatientcohort AT ueharanatsumi mutationalspectrumandclinicalfeaturesofpatientswithloxhd1variantsidentifiedinan8074hearinglosspatientcohort AT usamishinichi mutationalspectrumandclinicalfeaturesofpatientswithloxhd1variantsidentifiedinan8074hearinglosspatientcohort |