KSPublications - Mutations in LOXHD1, an Evolutionarily Conserved...

Title

Mutations in LOXHD1, an Evolutionarily Conserved Stereociliary Protein, Disrupt Hair Cell Function in Mice and Cause Progressive Hearing Loss in Humans

Authors

Nicolas Grillet et al.

Abstract

Hearing loss is the most common form of sensory impairment in humans and is frequently progressive in nature. Here we link a previously uncharacterized gene to hearing impairment in mice and humans. We show that hearing loss in the ethylnitrosourea (ENU)-induced samba mouse line is caused by a mutation in Loxhd1. LOXHD1 consists entirely of PLAT (polycystin/lipoxygenase/ -toxin) domains and is expressed along the membrane of mature hair cell stereocilia. Stereociliary development is unaffected in samba mice, but hair cell function is perturbed and hair cells eventually degenerate. Based on the studies in mice, we screened DNA from human families segregating deafness and identified a mutation in LOXHD1, which causes DFNB77, a progressive form of autosomal-recessive nonsyndromic hearing loss (ARNSHL). LOXHD1, MYO3a, and PJVK are the only human genes to date linked to progressive ARNSHL. These three genes are required for hair cell function, suggesting that age-dependent hair cell failure is a common mechanism for progressive ARNSHL.

Journal

AJHG

Date

9/4/2009

Link

PDF

Reference

Mutations in LOXHD1, an Evolutionarily Conserved Stereociliary Protein, Disrupt Hair Cell Function in Mice and Cause Progressive Hearing Loss in Humans

Nicolas Grillet¹^,¹¹, Martin Schwander¹^,¹¹, Michael S. Hildebrand², Anna Sczaniecka¹, Anand Kolatkar¹, Janice Velasco³, Jennifer A. Webster⁴, Kimia Kahrizi⁵, Hossein Najmabadi⁵, William J. Kimberling⁶, Dietrich Stephan³^,⁷^,⁸, Melanie Bahlo⁹, Tim Wiltshire¹⁰, Lisa M. Tarantino¹⁰, Peter Kuhn¹, Richard J.H. Smith² and Ulrich Müller¹^,

PMID

Keyword

TSRI Number

Attachments

Kuhn Lab at The Scripps Research Institute.