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

15 Citations (Scopus)

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
StatePublished - Sep 25 2000

Fingerprint

Deafness
Hearing Loss
Stereocilia
Microfilament Proteins
Actin Cytoskeleton
Radiation Hybrid Mapping
Genes
Synteny
Single-Stranded Conformational Polymorphism
Mutation
Sensorineural Hearing Loss
Inner Ear
Fluorescent Antibody Technique
Complementary DNA
Chromosomes

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

2E4/Kaptin (KPTN) - A candidate gene for the hearing loss locus, DFNA4. / Bearer, Elaine L.; Chen, A. F.; Chen, Hung Chih; Li, Z.; Mark, H. F.; Smith, R. J.H.; Jackson, C. L.

In: Annals of Human Genetics, Vol. 64, No. 3, 25.09.2000, p. 189-196.

Research output: Contribution to journalArticle

Bearer, EL, Chen, AF, Chen, HC, Li, Z, Mark, HF, Smith, RJH & Jackson, CL 2000, '2E4/Kaptin (KPTN) - A candidate gene for the hearing loss locus, DFNA4', Annals of Human Genetics, vol. 64, no. 3, pp. 189-196. https://doi.org/10.1017/S0003480000008071
Bearer EL, Chen AF, Chen HC, Li Z, Mark HF, Smith RJH et al. 2E4/Kaptin (KPTN) - A candidate gene for the hearing loss locus, DFNA4. Annals of Human Genetics. 2000 Sep 25;64(3):189-196. https://doi.org/10.1017/S0003480000008071
Bearer, Elaine L. ; Chen, A. F. ; Chen, Hung Chih ; Li, Z. ; Mark, H. F. ; Smith, R. J.H. ; Jackson, C. L. / 2E4/Kaptin (KPTN) - A candidate gene for the hearing loss locus, DFNA4. In: Annals of Human Genetics. 2000 ; Vol. 64, No. 3. pp. 189-196.
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