PUBLICATION

Mutations in OTOGL, Encoding the Inner Ear Protein Otogelin-like, Cause Moderate Sensorineural Hearing Loss

Authors
Yariz, K.O., Duman, D., Seco, C.Z., Dallman, J., Huang, M., Peters, T.A., Sirmaci, A., Lu, N., Schraders, M., Skromne, I., Oostrik, J., Diaz-Horta, O., Young, J.I., Tokgoz-Yilmaz, S., Konukseven, O., Shahin, H., Hetterschijt, L., Kanaan, M., Oonk, A.M., Edwards, Y.J., Li, H., Atalay, S., Blanton, S., Desmidt, A.A., Liu, X.Z., Pennings, R.J., Lu, Z., Chen, Z.Y., Kremer, H., and Tekin, M.
ID
ZDB-PUB-121121-14
Date
2012
Source
American journal of human genetics   91(5): 872-882 (Journal)
Registered Authors
Dallman, Julia, Skromne, Isaac
Keywords
none
MeSH Terms
  • Hearing Loss, Sensorineural/diagnosis
  • Hearing Loss, Sensorineural/genetics*
  • Child, Preschool
  • Zebrafish
  • INDEL Mutation
  • Adolescent
  • Cochlea/metabolism
  • Cochlea/pathology
  • Chromosome Aberrations
  • Male
  • Humans
  • Gene Expression Profiling
  • Gene Knockdown Techniques
  • Membrane Proteins/genetics*
  • Mutation*
  • Polymorphism, Single Nucleotide
  • Mice
  • Exome
  • Rats
  • Animals
(all 20)
PubMed
23122586 Full text @ Am. J. Hum. Genet.
Abstract

Hereditary hearing loss is characterized by a high degree of genetic heterogeneity. Here we present OTOGL mutations, a homozygous one base pair deletion (c.1430 delT) causing a frameshift (p.Val477Glufs25) in a large consanguineous family and two compound heterozygous mutations, c.547C>T (p.Arg183) and c.5238+5G>A, in a nonconsanguineous family with moderate nonsyndromic sensorineural hearing loss. OTOGL maps to the DFNB84 locus at 12q21.31 and encodes otogelin-like, which has structural similarities to the epithelial-secreted mucin protein family. We demonstrate that Otogl is expressed in the inner ear of vertebrates with a transcription level that is high in embryonic, lower in neonatal, and much lower in adult stages. Otogelin-like is localized to the acellular membranes of the cochlea and the vestibular system and to a variety of inner ear cells located underneath these membranes. Knocking down of otogl with morpholinos in zebrafish leads to sensorineural hearing loss and anatomical changes in the inner ear, supporting that otogelin-like is essential for normal inner ear function. We propose that OTOGL mutations affect the production and/or function of acellular structures of the inner ear, which ultimately leads to sensorineural hearing loss.

Genes / Markers
Figures
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Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
otoglWTstandard conditionsPrim-25ISH
otoglWTstandard conditionsLong-pecISH
1 - 2 of 2
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Phenotype
Fish Conditions Stage Phenotype Figure
WT + MO2-otoglstandard conditionsLong-pec
WT + MO2-otoglstandard conditionsLong-pec
WT + MO2-otoglstandard conditionsLong-pec
WT + MO2-otoglstandard conditionsLong-pec
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
sqet4EtTransgenic Insertion
    1 - 1 of 1
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    Human Disease / Model
    Sequence Targeting Reagents
    Fish
    Antibodies
    Orthology
    Engineered Foreign Genes
    Marker Marker Type Name
    EGFPEFGEGFP
    1 - 1 of 1
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    Mapping
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    Citation
    Yariz, K.O., Duman, D., Seco, C.Z., Dallman, J., Huang, M., Peters, T.A., Sirmaci, A., Lu, N., Schraders, M., Skromne, I., Oostrik, J., Diaz-Horta, O., Young, J.I., Tokgoz-Yilmaz, S., Konukseven, O., Shahin, H., Hetterschijt, L., Kanaan, M., Oonk, A.M., Edwards, Y.J., Li, H., Atalay, S., Blanton, S., Desmidt, A.A., Liu, X.Z., Pennings, R.J., Lu, Z., Chen, Z.Y., Kremer, H., and Tekin, M. (2012) Mutations in OTOGL, Encoding the Inner Ear Protein Otogelin-like, Cause Moderate Sensorineural Hearing Loss. American journal of human genetics. 91(5):872-882.