Mutations of the RDX gene cause nonsyndromic hearing loss at the DFNB24 locus

Shahid Khan, Zubair M. Ahmed, Muhammad I. Shabbir, Shin Ichiro Kitajiri, Saeeda Kalsoom, Saba Tasneem, Sara Shayiq, Arabandi Ramesh, Srikumari Srisailpathy, Shaheen N. Khan, Richard J.H. Smith, Saima Riazuddin, Thomas B. Friedman, Sheikh Riazuddin

Research output: Contribution to journalArticle

Abstract

Ezrin, radixin, and moesin are paralogous proteins that make up the ERM family and function as cross-linkers between integral membrane proteins and actin filaments of the cytoskeleton. In the mouse, a null allele of Rdx encoding radixin is associated with hearing loss as a result of the degeneration of inner ear hair cells as well as with hyperbilirubinemia due to hepatocyte dysfunction. Two mutant alleles of RDX [c.1732G > A (p.D578N) and c.1404_1405insG (p.A469fsX487)] segregating in two consanguineous Pakistani families are associated with neurosensory hearing loss. Both of these mutant alleles are predicted to affect the actin-binding motif of radixin. Sequence analysis of RDX in the DNA samples from the original DFNB24 family revealed a C.463C > T transition substitution that is predicted to truncate the protein in the FERM domain (F for 4.1, E for ezrin, R for radixin, and M for moesin) (p.Q155X). We also report a more complete gene and protein structure of RDX, including four additional exons and five new isoforms of RDX that are expressed in human retina and inner ear. Further, high-resolution confocal microscopy in mouse inner ear demonstrates that radixin is expressed along the length of stereocilia of hair cells from both the organ of Corti and the vestibular system.

Original languageEnglish (US)
Pages (from-to)417-423
Number of pages7
JournalHuman mutation
Volume28
Issue number5
DOIs
StatePublished - May 1 2007
Externally publishedYes

Fingerprint

Inner Ear
Mutation
Genes
Alleles
Actin Cytoskeleton
Hearing Loss
Inner Auditory Hair Cells
Stereocilia
Organ of Corti
Proteins
Hyperbilirubinemia
Confocal Microscopy
Sequence Analysis
Retina
Actins
Hepatocytes
Exons
Protein Isoforms
Membrane Proteins
cyclonite

Keywords

  • Cytoskeleton
  • Deafness
  • ERM
  • Ezrin
  • Hair cells
  • Nonsyndromic hearing loss
  • Radixin
  • RDX
  • Stereocilia

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Khan, S., Ahmed, Z. M., Shabbir, M. I., Kitajiri, S. I., Kalsoom, S., Tasneem, S., ... Riazuddin, S. (2007). Mutations of the RDX gene cause nonsyndromic hearing loss at the DFNB24 locus. Human mutation, 28(5), 417-423. https://doi.org/10.1002/humu.20469

Mutations of the RDX gene cause nonsyndromic hearing loss at the DFNB24 locus. / Khan, Shahid; Ahmed, Zubair M.; Shabbir, Muhammad I.; Kitajiri, Shin Ichiro; Kalsoom, Saeeda; Tasneem, Saba; Shayiq, Sara; Ramesh, Arabandi; Srisailpathy, Srikumari; Khan, Shaheen N.; Smith, Richard J.H.; Riazuddin, Saima; Friedman, Thomas B.; Riazuddin, Sheikh.

In: Human mutation, Vol. 28, No. 5, 01.05.2007, p. 417-423.

Research output: Contribution to journalArticle

Khan, S, Ahmed, ZM, Shabbir, MI, Kitajiri, SI, Kalsoom, S, Tasneem, S, Shayiq, S, Ramesh, A, Srisailpathy, S, Khan, SN, Smith, RJH, Riazuddin, S, Friedman, TB & Riazuddin, S 2007, 'Mutations of the RDX gene cause nonsyndromic hearing loss at the DFNB24 locus', Human mutation, vol. 28, no. 5, pp. 417-423. https://doi.org/10.1002/humu.20469
Khan S, Ahmed ZM, Shabbir MI, Kitajiri SI, Kalsoom S, Tasneem S et al. Mutations of the RDX gene cause nonsyndromic hearing loss at the DFNB24 locus. Human mutation. 2007 May 1;28(5):417-423. https://doi.org/10.1002/humu.20469
Khan, Shahid ; Ahmed, Zubair M. ; Shabbir, Muhammad I. ; Kitajiri, Shin Ichiro ; Kalsoom, Saeeda ; Tasneem, Saba ; Shayiq, Sara ; Ramesh, Arabandi ; Srisailpathy, Srikumari ; Khan, Shaheen N. ; Smith, Richard J.H. ; Riazuddin, Saima ; Friedman, Thomas B. ; Riazuddin, Sheikh. / Mutations of the RDX gene cause nonsyndromic hearing loss at the DFNB24 locus. In: Human mutation. 2007 ; Vol. 28, No. 5. pp. 417-423.
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AU - Khan, Shahid

AU - Ahmed, Zubair M.

AU - Shabbir, Muhammad I.

AU - Kitajiri, Shin Ichiro

AU - Kalsoom, Saeeda

AU - Tasneem, Saba

AU - Shayiq, Sara

AU - Ramesh, Arabandi

AU - Srisailpathy, Srikumari

AU - Khan, Shaheen N.

AU - Smith, Richard J.H.

AU - Riazuddin, Saima

AU - Friedman, Thomas B.

AU - Riazuddin, Sheikh

PY - 2007/5/1

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N2 - Ezrin, radixin, and moesin are paralogous proteins that make up the ERM family and function as cross-linkers between integral membrane proteins and actin filaments of the cytoskeleton. In the mouse, a null allele of Rdx encoding radixin is associated with hearing loss as a result of the degeneration of inner ear hair cells as well as with hyperbilirubinemia due to hepatocyte dysfunction. Two mutant alleles of RDX [c.1732G > A (p.D578N) and c.1404_1405insG (p.A469fsX487)] segregating in two consanguineous Pakistani families are associated with neurosensory hearing loss. Both of these mutant alleles are predicted to affect the actin-binding motif of radixin. Sequence analysis of RDX in the DNA samples from the original DFNB24 family revealed a C.463C > T transition substitution that is predicted to truncate the protein in the FERM domain (F for 4.1, E for ezrin, R for radixin, and M for moesin) (p.Q155X). We also report a more complete gene and protein structure of RDX, including four additional exons and five new isoforms of RDX that are expressed in human retina and inner ear. Further, high-resolution confocal microscopy in mouse inner ear demonstrates that radixin is expressed along the length of stereocilia of hair cells from both the organ of Corti and the vestibular system.

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KW - Hair cells

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KW - RDX

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