Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss

Publication Date:
2018-04-28
Publisher:
BMJ Publishing Group
Print ISSN:
0022-2593
Electronic ISSN:
1468-6244
Topics:
Medicine
Keywords:
Open access
Published by:
http://www.bmj.com/
_version_ 1839208032940064768
autor Gao, X., Yuan, Y.-Y., Lin, Q.-F., Xu, J.-C., Wang, W.-Q., Qiao, Y.-H., Kang, D.-Y., Bai, D., Xin, F., Huang, S.-S., Qiu, S.-W., Guan, L.-P., Su, Y., Wang, G.-J., Han, M.-Y., Jiang, Y., Liu, H.-K., Dai, P.
beschreibung Background Hereditary sensorineural hearing loss is a genetically heterogeneous disorder. Objectives This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL). Methods Whole exome sequencing and linkage analysis were performed to identify pathogenic mutation. Inner ear expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1 Morpholino knockdown Zebrafish were constructed to explore the deafness mechanism. Results We identified a cosegregating heterozygous missense mutation, c.296G〉A (p.Arg99His) in the gene encoding interferon lambda receptor 1 ( IFNLR1 ) – a protein that functions in the Jak/ STAT pathway– are associated with ADNSHL . Morpholino knockdown of ifnlr1 leads to a significant decrease in hair cells and non-inflation of the swim bladder in late-stage zebrafish, which can be reversed by injection with normal Zebrafish ifnlr1 mRNA. Knockdown of ifnlr1 in zebrafish causes significant upregulation of cytokine receptor family member b4 (interleukin-10r2), jak1, tyrosine kinase 2, stat3, and stat5b in the Jak1/STAT3 pathway at the mRNA level. Conclusion IFNLR1 function is required in the auditory system and that IFNLR1 mutations are associated with ADNSHL. To the best of our knowledge, this is the first study implicating an interferon lambda receptor in auditory function.
citation_standardnr 6246591
datenlieferant ipn_articles
feed_id 5627
feed_publisher BMJ Publishing Group
feed_publisher_url http://www.bmj.com/
insertion_date 2018-04-28
journaleissn 1468-6244
journalissn 0022-2593
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher BMJ Publishing Group
quelle Journal of Medical Genetics
relation http://jmg.bmj.com/cgi/content/short/55/5/298?rss=1
schlagwort Open access
search_space articles
shingle_author_1 Gao, X., Yuan, Y.-Y., Lin, Q.-F., Xu, J.-C., Wang, W.-Q., Qiao, Y.-H., Kang, D.-Y., Bai, D., Xin, F., Huang, S.-S., Qiu, S.-W., Guan, L.-P., Su, Y., Wang, G.-J., Han, M.-Y., Jiang, Y., Liu, H.-K., Dai, P.
shingle_author_2 Gao, X., Yuan, Y.-Y., Lin, Q.-F., Xu, J.-C., Wang, W.-Q., Qiao, Y.-H., Kang, D.-Y., Bai, D., Xin, F., Huang, S.-S., Qiu, S.-W., Guan, L.-P., Su, Y., Wang, G.-J., Han, M.-Y., Jiang, Y., Liu, H.-K., Dai, P.
shingle_author_3 Gao, X., Yuan, Y.-Y., Lin, Q.-F., Xu, J.-C., Wang, W.-Q., Qiao, Y.-H., Kang, D.-Y., Bai, D., Xin, F., Huang, S.-S., Qiu, S.-W., Guan, L.-P., Su, Y., Wang, G.-J., Han, M.-Y., Jiang, Y., Liu, H.-K., Dai, P.
shingle_author_4 Gao, X., Yuan, Y.-Y., Lin, Q.-F., Xu, J.-C., Wang, W.-Q., Qiao, Y.-H., Kang, D.-Y., Bai, D., Xin, F., Huang, S.-S., Qiu, S.-W., Guan, L.-P., Su, Y., Wang, G.-J., Han, M.-Y., Jiang, Y., Liu, H.-K., Dai, P.
shingle_catch_all_1 Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss
Open access
Background Hereditary sensorineural hearing loss is a genetically heterogeneous disorder. Objectives This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL). Methods Whole exome sequencing and linkage analysis were performed to identify pathogenic mutation. Inner ear expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1 Morpholino knockdown Zebrafish were constructed to explore the deafness mechanism. Results We identified a cosegregating heterozygous missense mutation, c.296G>A (p.Arg99His) in the gene encoding interferon lambda receptor 1 ( IFNLR1 ) – a protein that functions in the Jak/ STAT pathway– are associated with ADNSHL . Morpholino knockdown of ifnlr1 leads to a significant decrease in hair cells and non-inflation of the swim bladder in late-stage zebrafish, which can be reversed by injection with normal Zebrafish ifnlr1 mRNA. Knockdown of ifnlr1 in zebrafish causes significant upregulation of cytokine receptor family member b4 (interleukin-10r2), jak1, tyrosine kinase 2, stat3, and stat5b in the Jak1/STAT3 pathway at the mRNA level. Conclusion IFNLR1 function is required in the auditory system and that IFNLR1 mutations are associated with ADNSHL. To the best of our knowledge, this is the first study implicating an interferon lambda receptor in auditory function.
Gao, X., Yuan, Y.-Y., Lin, Q.-F., Xu, J.-C., Wang, W.-Q., Qiao, Y.-H., Kang, D.-Y., Bai, D., Xin, F., Huang, S.-S., Qiu, S.-W., Guan, L.-P., Su, Y., Wang, G.-J., Han, M.-Y., Jiang, Y., Liu, H.-K., Dai, P.
BMJ Publishing Group
0022-2593
00222593
1468-6244
14686244
shingle_catch_all_2 Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss
Open access
Background Hereditary sensorineural hearing loss is a genetically heterogeneous disorder. Objectives This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL). Methods Whole exome sequencing and linkage analysis were performed to identify pathogenic mutation. Inner ear expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1 Morpholino knockdown Zebrafish were constructed to explore the deafness mechanism. Results We identified a cosegregating heterozygous missense mutation, c.296G>A (p.Arg99His) in the gene encoding interferon lambda receptor 1 ( IFNLR1 ) – a protein that functions in the Jak/ STAT pathway– are associated with ADNSHL . Morpholino knockdown of ifnlr1 leads to a significant decrease in hair cells and non-inflation of the swim bladder in late-stage zebrafish, which can be reversed by injection with normal Zebrafish ifnlr1 mRNA. Knockdown of ifnlr1 in zebrafish causes significant upregulation of cytokine receptor family member b4 (interleukin-10r2), jak1, tyrosine kinase 2, stat3, and stat5b in the Jak1/STAT3 pathway at the mRNA level. Conclusion IFNLR1 function is required in the auditory system and that IFNLR1 mutations are associated with ADNSHL. To the best of our knowledge, this is the first study implicating an interferon lambda receptor in auditory function.
Gao, X., Yuan, Y.-Y., Lin, Q.-F., Xu, J.-C., Wang, W.-Q., Qiao, Y.-H., Kang, D.-Y., Bai, D., Xin, F., Huang, S.-S., Qiu, S.-W., Guan, L.-P., Su, Y., Wang, G.-J., Han, M.-Y., Jiang, Y., Liu, H.-K., Dai, P.
BMJ Publishing Group
0022-2593
00222593
1468-6244
14686244
shingle_catch_all_3 Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss
Open access
Background Hereditary sensorineural hearing loss is a genetically heterogeneous disorder. Objectives This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL). Methods Whole exome sequencing and linkage analysis were performed to identify pathogenic mutation. Inner ear expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1 Morpholino knockdown Zebrafish were constructed to explore the deafness mechanism. Results We identified a cosegregating heterozygous missense mutation, c.296G>A (p.Arg99His) in the gene encoding interferon lambda receptor 1 ( IFNLR1 ) – a protein that functions in the Jak/ STAT pathway– are associated with ADNSHL . Morpholino knockdown of ifnlr1 leads to a significant decrease in hair cells and non-inflation of the swim bladder in late-stage zebrafish, which can be reversed by injection with normal Zebrafish ifnlr1 mRNA. Knockdown of ifnlr1 in zebrafish causes significant upregulation of cytokine receptor family member b4 (interleukin-10r2), jak1, tyrosine kinase 2, stat3, and stat5b in the Jak1/STAT3 pathway at the mRNA level. Conclusion IFNLR1 function is required in the auditory system and that IFNLR1 mutations are associated with ADNSHL. To the best of our knowledge, this is the first study implicating an interferon lambda receptor in auditory function.
Gao, X., Yuan, Y.-Y., Lin, Q.-F., Xu, J.-C., Wang, W.-Q., Qiao, Y.-H., Kang, D.-Y., Bai, D., Xin, F., Huang, S.-S., Qiu, S.-W., Guan, L.-P., Su, Y., Wang, G.-J., Han, M.-Y., Jiang, Y., Liu, H.-K., Dai, P.
BMJ Publishing Group
0022-2593
00222593
1468-6244
14686244
shingle_catch_all_4 Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss
Open access
Background Hereditary sensorineural hearing loss is a genetically heterogeneous disorder. Objectives This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL). Methods Whole exome sequencing and linkage analysis were performed to identify pathogenic mutation. Inner ear expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1 Morpholino knockdown Zebrafish were constructed to explore the deafness mechanism. Results We identified a cosegregating heterozygous missense mutation, c.296G>A (p.Arg99His) in the gene encoding interferon lambda receptor 1 ( IFNLR1 ) – a protein that functions in the Jak/ STAT pathway– are associated with ADNSHL . Morpholino knockdown of ifnlr1 leads to a significant decrease in hair cells and non-inflation of the swim bladder in late-stage zebrafish, which can be reversed by injection with normal Zebrafish ifnlr1 mRNA. Knockdown of ifnlr1 in zebrafish causes significant upregulation of cytokine receptor family member b4 (interleukin-10r2), jak1, tyrosine kinase 2, stat3, and stat5b in the Jak1/STAT3 pathway at the mRNA level. Conclusion IFNLR1 function is required in the auditory system and that IFNLR1 mutations are associated with ADNSHL. To the best of our knowledge, this is the first study implicating an interferon lambda receptor in auditory function.
Gao, X., Yuan, Y.-Y., Lin, Q.-F., Xu, J.-C., Wang, W.-Q., Qiao, Y.-H., Kang, D.-Y., Bai, D., Xin, F., Huang, S.-S., Qiu, S.-W., Guan, L.-P., Su, Y., Wang, G.-J., Han, M.-Y., Jiang, Y., Liu, H.-K., Dai, P.
BMJ Publishing Group
0022-2593
00222593
1468-6244
14686244
shingle_title_1 Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss
shingle_title_2 Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss
shingle_title_3 Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss
shingle_title_4 Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss
timestamp 2025-07-31T23:44:23.473Z
titel Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss
titel_suche Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss
topic WW-YZ
uid ipn_articles_6246591