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- Title
Auditory neuropathy in patients carrying mutations in the otoferlin gene (OTOF)(Communicated by Xavier Estivill).
- Authors
Montserrat Rodríguez-Ballesteros; Francisco J. del Castillo; Yolanda Martín; Miguel A. Moreno-Pelayo; Constantino Morera; Félix Prieto; Jaime Marco; Antonio Morant; Jaime Gallo-Terán; Carmelo Morales-Angulo; Cristina Navas; Germán Trinidad; M. Cruz Tapia; Felipe Moreno; Ignacio del Castillo
- Abstract
Inherited hearing impairment affects one in 2,000 newborns. Nonsyndromic prelingual forms are inherited mainly as autosomal recessive traits, for which 16 genes are currently known. Mutations in the genes encoding connexins 26 and 30 account for up to 50% of these cases. However, the individual contribution of the remaining genes to the whole remains undetermined. In addition, for most of the genes there is a need for studies on genotypephenotype correlations, to identify distinctive clinical features which may direct the molecular diagnosis to specific genes. Here we present a mutation analysis and a genotypephenotype correlation study on the gene encoding otoferlin (OTOF), responsible for the DFNB9 subtype of prelingual hearing impairment. Four novel mutations were identified: c.2122C>T (p.Arg708Ter), c.4275G>A (p.Trp1425Ter), c.4362+2T>G, and c.5860_5862delATC (p.Ile1954del). A total of 37 subjects with muta-tions in OTOF were studied clinically. They were phenotypically homogeneous, having profound hearing impairment with very early onset, as shown by pure-tone audiometry and auditory brainstem responses. Magnetic resonance imaging and computed tomography did not reveal any inner ear malformation. Unexpectedly, transient evoked otoacoustic emissions (TEOAEs) were present, either bilaterally or unilaterally in 11 subjects. Altogether, clinical data of these subjects met the diagnostic criteria of auditory neuropathy. A total of 10 subjects had been successfully provided with cochlear implants. The results of our study indicate that genetic diagnosis of subjects with auditory neuropathy and profound hearing impairment should be directed to the otoferlin gene. Our data are of concern to universal screening programs which use TEOAEs as the first detection test for hearing impairment in newborns, since this technique may overlook a nonnegligible proportion of cases. Hum Mutat 22:451456, 2003. © 2003 Wiley-Liss, Inc.
- Subjects
GENETIC disorders; GENETIC mutation; GENES; HEARING disorders; NEONATAL diseases
- Publication
Human Mutation, 2003, Vol 22, Issue 6, p451
- ISSN
1059-7794
- Publication type
Article