Mutations of the RDX gene cause nonsyndromic hearing loss at the DFNB24 locus.
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.
Khan
Shahid Y
SY
National Centre of Excellence in Molecular Biology, Punjab University, Lahore, Pakistan.
Ahmed
Zubair M
ZM
Shabbir
Muhammad I
MI
Kitajiri
Shin-ichiro
S
Kalsoom
Saeeda
S
Tasneem
Saba
S
Shayiq
Sara
S
Ramesh
Arabandi
A
Srisailpathy
Srikumari
S
Khan
Shaheen N
SN
Smith
Richard J H
RJ
Riazuddin
Saima
S
Friedman
Thomas B
TB
Riazuddin
Sheikh
S
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers; D007758:Ear, Inner / Q000378:metabolism; D005091:Exons; D008040:Genetic Linkage; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009154:Mutation; D010154:Pakistan; D010375:Pedigree; D012160:Retina / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D003598:Cytoskeletal Proteins; D017931:DNA Primers; D008565:Membrane Proteins; C071776:radixin