Premium
Mutations of the RDX gene cause nonsyndromic hearing loss at the DFNB24 locus
Author(s) -
Khan Shahid Y.,
Ahmed Zubair M.,
Shabbir Muhammad I.,
Kitajiri Shinichiro,
Kalsoom Saeeda,
Tasneem Saba,
Shayiq Sara,
Ramesh Arabandi,
Srisailpathy Srikumari,
Khan Shaheen N.,
Smith Richard J.H.,
Riazuddin Saima,
Friedman Thomas B.,
Riazuddin Sheikh
Publication year - 2007
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20469
Subject(s) - radixin , moesin , biology , inner ear , genetics , hearing loss , locus (genetics) , allele , stereocilia (inner ear) , mutant , exon , microbiology and biotechnology , ezrin , gene , hair cell , cytoskeleton , anatomy , medicine , cell , audiology
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. Hum Mutat 28(5), 417–423, 2007. Published 2007 Wiley‐Liss, Inc.