Mutations of the RDX gene cause nonsyndromic hearing loss at the DFNB24 locus.
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Khan SY, Ahmed ZM, Shabbir MI, Kitajiri S, Kalsoom S, Tasneem S, Shayiq S, Ramesh A, Srisailpathy S, Khan SN, Smith RJ, Riazuddin S, Friedman TB, Riazuddin S
Mutations of the RDX gene cause nonsyndromic hearing loss at the DFNB24 locus.
Hum Mutat. 2007 May;28(5):417-23.
- PubMed ID
- 17226784 [ View in PubMed]
- 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.