2E4/Kaptin (KPTN) - A candidate gene for the hearing loss locus, DFNA4

Elaine L. Bearer, A. F. Chen, Hung Chih Chen, Z. Li, H. F. Mark, R. J.H. Smith, C. L. Jackson

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Stereocilia of the inner ear play an integral role in the mechanotransduction of sound. Their structural support is derived from actin filaments and actin-binding proteins. We have identified a novel actin-binding protein, 2E4-kaptin (KPTN), which appears to be involved in this structural network. Using double label immunofluorescence, we now show that KPTN extends beyond the barbed ends of actin filaments at the tips of stereocilia, and using cloned human cDNA, we mapped KPTN to chromosome 19q13.4. A combination of FISH, radiation hybrid mapping and YAC screening localized KPTN between markers D19S412 and NIB1805, making this gene an excellent functional and positional candidate for DFNA4, a form of autosomal dominant non-syndromic hearing loss. We identified a second family with inherited deafness that also maps to the DFNA4 region. To screen KPTN for deafness-causing mutations, we first determined its genomic structure and then completed a mutational analysis by direct sequencing and SSCP in affected family members. Although no deafness-causing mutations were identified in the coding region, KPTN remains an excellent candidate gene for hearing loss; by synteny, its murine orthologue also remains a candidate gene for the Nijmegan waltzer (nv) mouse mutant, which has vestibular defects and a variable sensorineural hearing loss.

Original languageEnglish (US)
Pages (from-to)189-196
Number of pages8
JournalAnnals of Human Genetics
Volume64
Issue number3
DOIs
Publication statusPublished - Sep 25 2000

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Bearer, E. L., Chen, A. F., Chen, H. C., Li, Z., Mark, H. F., Smith, R. J. H., & Jackson, C. L. (2000). 2E4/Kaptin (KPTN) - A candidate gene for the hearing loss locus, DFNA4. Annals of Human Genetics, 64(3), 189-196. https://doi.org/10.1017/S0003480000008071