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

Shahid Y 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; Thomas B Friedman; Sheikh Riazuddin; Saima Riazuddin

doi:10.1002/humu.20469

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

Journal article

Open access

Peer reviewed

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

Shahid Y Khan, Zubair M Ahmed, Muhammad I Shabbir, Shin-ichiro Kitajiri, Saeeda Kalsoom, Saba Tasneem, Sara Shayiq, Arabandi Ramesh, Srikumari Srisailpathy, Shaheen N Khan, …

Human mutation, Vol.28(5), pp.417-423

05/2007

DOI: 10.1002/humu.20469

PMID: 17226784

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https://zenodo.org/record/1229192View

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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.

Pakistan

Mutation

Retina - metabolism

Cytoskeletal Proteins - genetics

Exons

Humans

Molecular Sequence Data

Base Sequence

Cloning, Molecular

Cytoskeletal Proteins - metabolism

Membrane Proteins - metabolism

Genetic Linkage

Amino Acid Sequence

Membrane Proteins - genetics

Mice, Inbred C57BL

Chromosome Mapping

DNA Primers

Hearing Loss - genetics

Sequence Homology, Amino Acid

Microscopy, Confocal

Ear, Inner - metabolism

Animals

Pedigree

Alleles

Chromosomes, Human, Pair 11

Mice

Details

Title: Subtitle: Mutations of the RDX gene cause nonsyndromic hearing loss at the DFNB24 locus
Creators: Shahid Y Khan - National Centre of Excellence in Molecular Biology, Punjab University, Lahore, Pakistan
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
Thomas B Friedman
Sheikh Riazuddin
Saima Riazuddin
Resource Type: Journal article
Publication Details: Human mutation, Vol.28(5), pp.417-423
DOI: 10.1002/humu.20469
PMID: 17226784
NLM abbreviation: Hum Mutat
ISSN: 1059-7794
eISSN: 1098-1004
Publisher: United States
Grant note: R01-DC02842 / NIDCD NIH HHS Intramural NIH HHS
Language: English
Date published: 05/2007
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
Record Identifier: 9984007186602771

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