Gene structure, chromosomal localization, and mutation screening of the human gene for the inner ear protein otospiralin.
Otospiralin is a novel protein of unknown function that is produced by non-sensory cells (fibrocytes) of the inner ear (cochlea and vestibule). We showed that downregulation of otospiralin in guinea pigs leads to deafness and we therefore hypothesized that genetic defects in the otospiralin gene could also cause deafness in humans. In this study, we cloned and localized OTOSP, the human gene for otospiralin. OTOSP spans 1630 nucleotides, contains four exons and codes for a 567-nucleotide cDNA. By fluorescence in situ hybridization and hybrid panel mapping we localized OTOSP on chromosome 2 at position q37.3. There is currently no deafness family linked to this region. We screened OTOSP for mutations in 410 unrelated patients exhibiting various levels of hearing loss. Beside intronic polymorphisms, a rare variant (Pro7Leu) was found in 4 deafness patients and 3 control individuals, indicating that this change is not involved in this condition and excluding OTOSP as a major gene for genetic deafness.
Lavigne-Rebillard
Mireille
M
Physiopathologie et Thérapie des Déficits Sensoriels et Moteurs, INSERM U 583, 71 rue de Navacelles, 34090 Montpellier, France.
Delprat
Benjamin
B
Surget
Marie-Odile
MO
Griffoin
Jean-Michel
JM
Weil
Dominique
D
Arbones
Mariona
M
Vincent
Robert
R
Hamel
Christian P
CP
D019943:Amino Acid Substitution; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics; D005091:Exons / Q000235:genetics; D005796:Genes; D014644:Genetic Variation; D034381:Hearing Loss / Q000235:genetics; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D021382:Protein Sorting Signals / Q000235:genetics; D011506:Proteins / Q000235:genetics* / Q000502:physiology
C503045:OTOS protein, human; D021382:Protein Sorting Signals; D011506:Proteins