A biallelic variant in CLRN2 causes non-syndromic hearing loss in humans

  1. Vona, Barbara ORCID logo
  2. Mazaheri, Neda ORCID logo
  3. Lin, Sheng-Jia ORCID logo
  4. Dunbar, Lucy ORCID logo
  5. Maroofian, Reza
  6. Azaiez, Hela ORCID logo
  7. Booth, Kevin T. ORCID logo
  8. Vitry, Sandrine ORCID logo
  9. Rad, Abolfazl ORCID logo
  10. Rüschendorf, Franz ORCID logo
  11. Varshney, Pratishtha ORCID logo
  12. Fowler, Ben
  13. Beetz, Christian ORCID logo
  14. Alagramam, Kumar N.
  15. Murphy, David ORCID logo
  16. Shariati, Gholamreza
  17. Sedaghat, Alireza
  18. Houlden, Henry ORCID logo
  19. Petree, Cassidy ORCID logo
  20. VijayKumar, Shruthi ORCID logo
  21. Smith, Richard ORCID logo
  22. Haaf, Thomas ORCID logo
  23. EL-AMRAOUI, Aziz ORCID logo
  24. Bowl, Michael ORCID logo
  25. Varshney, Gaurav K. ORCID logo
  26. Galehdari, Hamid

Download
s00439-020-02254-z.pdf 7,37MB
WeightNameValue
1000 Titel
  • A biallelic variant in CLRN2 causes non-syndromic hearing loss in humans
1000 Autor/in
  1. Vona, Barbara |
  2. Mazaheri, Neda |
  3. Lin, Sheng-Jia |
  4. Dunbar, Lucy |
  5. Maroofian, Reza |
  6. Azaiez, Hela |
  7. Booth, Kevin T. |
  8. Vitry, Sandrine |
  9. Rad, Abolfazl |
  10. Rüschendorf, Franz |
  11. Varshney, Pratishtha |
  12. Fowler, Ben |
  13. Beetz, Christian |
  14. Alagramam, Kumar N. |
  15. Murphy, David |
  16. Shariati, Gholamreza |
  17. Sedaghat, Alireza |
  18. Houlden, Henry |
  19. Petree, Cassidy |
  20. VijayKumar, Shruthi |
  21. Smith, Richard |
  22. Haaf, Thomas |
  23. EL-AMRAOUI, Aziz |
  24. Bowl, Michael |
  25. Varshney, Gaurav K. |
  26. Galehdari, Hamid |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-01-26
1000 Erschienen in
1000 Quellenangabe
  • 140(6):915-931
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00439-020-02254-z |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099798/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Deafness, the most frequent sensory deficit in humans, is extremely heterogeneous with hundreds of genes involved. Clinical and genetic analyses of an extended consanguineous family with pre-lingual, moderate-to-profound autosomal recessive sensorineural hearing loss, allowed us to identify CLRN2, encoding a tetraspan protein, as a new deafness gene. Homozygosity mapping followed by exome sequencing identified a 14.96 Mb locus on chromosome 4p15.32p15.1 containing a likely pathogenic missense variant in CLRN2 (c.494C > A, NM_001079827.2) segregating with the disease. Using in vitro RNA splicing analysis, we show that the CLRN2 c.494C > A variant leads to two events: (1) the substitution of a highly conserved threonine (uncharged amino acid) to lysine (charged amino acid) at position 165, p.(Thr165Lys), and (2) aberrant splicing, with the retention of intron 2 resulting in a stop codon after 26 additional amino acids, p.(Gly146Lysfs*26). Expression studies and phenotyping of newly produced zebrafish and mouse models deficient for clarin 2 further confirm that clarin 2, expressed in the inner ear hair cells, is essential for normal organization and maintenance of the auditory hair bundles, and for hearing function. Together, our findings identify CLRN2 as a new deafness gene, which will impact future diagnosis and treatment for deaf patients.
1000 Sacherschließung
lokal Chromosome Mapping [MeSH]
lokal Membrane Proteins/deficiency [MeSH]
lokal Molecular Medicine
lokal Gene Expression [MeSH]
lokal Original Investigation
lokal Zebrafish [MeSH]
lokal Male [MeSH]
lokal Base Sequence [MeSH]
lokal Tetraspanins/deficiency [MeSH]
lokal Hearing Loss, Sensorineural/genetics [MeSH]
lokal Point Mutation [MeSH]
lokal Human Genetics
lokal Membrane Proteins/genetics [MeSH]
lokal Consanguinity [MeSH]
lokal Female [MeSH]
lokal Hair Cells, Auditory, Inner/metabolism [MeSH]
lokal Hearing Loss, Sensorineural/pathology [MeSH]
lokal Amino Acid Substitution [MeSH]
lokal Adult [MeSH]
lokal Humans [MeSH]
lokal Hearing Loss, Sensorineural/metabolism [MeSH]
lokal Whole Exome Sequencing [MeSH]
lokal Chromosomes, Human, Pair 4/chemistry [MeSH]
lokal Animals [MeSH]
lokal Mice [MeSH]
lokal Pedigree [MeSH]
lokal Metabolic Diseases
lokal Genes, Recessive [MeSH]
lokal Gene Function
lokal Alleles [MeSH]
lokal Tetraspanins/genetics [MeSH]
lokal Hair Cells, Auditory, Inner/pathology [MeSH]
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-6719-3447|https://orcid.org/0000-0002-7638-5555|https://orcid.org/0000-0002-7559-6529|https://orcid.org/0000-0003-2129-9091|https://frl.publisso.de/adhoc/uri/TWFyb29maWFuLCBSZXph|https://orcid.org/0000-0002-2863-6970|https://orcid.org/0000-0003-3061-3652|https://orcid.org/0000-0003-4693-7694|https://orcid.org/0000-0001-8627-8828|https://orcid.org/0000-0001-5640-810X|https://orcid.org/0000-0002-2619-7775|https://frl.publisso.de/adhoc/uri/Rm93bGVyLCBCZW4=|https://orcid.org/0000-0001-7061-2895|https://frl.publisso.de/adhoc/uri/QWxhZ3JhbWFtLCBLdW1hciBOLg==|https://orcid.org/0000-0002-3771-3800|https://frl.publisso.de/adhoc/uri/U2hhcmlhdGksIEdob2xhbXJlemE=|https://frl.publisso.de/adhoc/uri/U2VkYWdoYXQsIEFsaXJlemE=|https://orcid.org/0000-0002-2866-7777|https://orcid.org/0000-0002-9379-2400|https://orcid.org/0000-0001-6679-1261|https://orcid.org/0000-0003-1201-6731|https://orcid.org/0000-0002-0737-0763|https://orcid.org/0000-0003-2692-4984|https://orcid.org/0000-0001-7971-445X|https://orcid.org/0000-0002-0429-1904|https://frl.publisso.de/adhoc/uri/R2FsZWhkYXJpLCBIYW1pZA==
1000 Hinweis
  • DeepGreen-ID: 780c7ac8f8004a65b99267b8da7b4baa ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
1000 Label
1000 Dateien
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6446844.rdf
1000 Erstellt am 2023-04-28T14:21:08.828+0200
1000 Erstellt von 322
1000 beschreibt frl:6446844
1000 Zuletzt bearbeitet 2023-10-20T19:06:49.473+0200
1000 Objekt bearb. Fri Oct 20 19:06:49 CEST 2023
1000 Vgl. frl:6446844
1000 Oai Id
  1. oai:frl.publisso.de:frl:6446844 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

View source