A truncating CLDN9 variant is associated with autosomal recessive nonsyndromic hearing loss

Claire J. Sineni, Muzeyyen Yildirim-Baylan, Shengru Guo, Vladimir Camarena, Gaofeng Wang, Suna Tokgoz-Yilmaz, Duygu Duman, Guney Bademci, Mustafa Tekin

Research output: Contribution to journalArticle

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Abstract

While the importance of tight junctions in hearing is well established, the role of Claudin- 9 (CLDN9), a tight junction protein, in human hearing and deafness has not been explored. Through whole-genome sequencing, we identified a one base pair deletion (c.86delT) in CLDN9 in a consanguineous family from Turkey with autosomal recessive nonsyndromic hearing loss. Three affected members of the family had sensorineural hearing loss (SNHL) ranging from moderate to profound in severity. The variant is predicted to cause a frameshift and produce a truncated protein (p.Leu29ArgfsTer4) in this single-exon gene. It is absent in public databases as well as in over 1000 Turkish individuals, and co-segregates with SNHL in the family. Our in vitro studies demonstrate that the mutant protein does not localize to cell membrane as demonstrated for the wild-type protein. Mice-lacking Cldn9 have been shown to develop SNHL. We conclude that CLDN9 is essential for proper audition in humans and its disruption leads to SNHL in humans.

Original languageEnglish (US)
JournalHuman Genetics
DOIs
StatePublished - Jan 1 2019

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Sensorineural Hearing Loss
Hearing
Tight Junction Proteins
Tight Junctions
Deafness
Mutant Proteins
Turkey
Base Pairing
Exons
Proteins
Cell Membrane
Genome
Databases
Nonsyndromic Deafness
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

A truncating CLDN9 variant is associated with autosomal recessive nonsyndromic hearing loss. / Sineni, Claire J.; Yildirim-Baylan, Muzeyyen; Guo, Shengru; Camarena, Vladimir; Wang, Gaofeng; Tokgoz-Yilmaz, Suna; Duman, Duygu; Bademci, Guney; Tekin, Mustafa.

In: Human Genetics, 01.01.2019.

Research output: Contribution to journalArticle

Sineni, Claire J. ; Yildirim-Baylan, Muzeyyen ; Guo, Shengru ; Camarena, Vladimir ; Wang, Gaofeng ; Tokgoz-Yilmaz, Suna ; Duman, Duygu ; Bademci, Guney ; Tekin, Mustafa. / A truncating CLDN9 variant is associated with autosomal recessive nonsyndromic hearing loss. In: Human Genetics. 2019.
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AU - Camarena, Vladimir

AU - Wang, Gaofeng

AU - Tokgoz-Yilmaz, Suna

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AU - Tekin, Mustafa

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