Temperature-sensitive auditory neuropathy associated with an otoferlin mutation: Deafening fever!
Transient deafness associated with an increase in core body temperature is a rare and puzzling disorder. Temperature-dependent deafness has been previously observed in patients suffering from auditory neuropathy. Auditory neuropathy is a clinical entity of sensorineural deafness characterized by absent auditory brainstem response and normal otoacoustic emissions. Mutations in OTOF, which encodes otoferlin, have been previously reported to cause DFNB9, a non-syndromic form of deafness characterized by severe to profound prelingual hearing impairment and auditory neuropathy. Here we report a novel mutation in OTOF gene in a large family affected by temperature-dependent auditory neuropathy. Three siblings aged 10, 9 and 7 years from a consanguineous family were found to be affected by severe or profound hearing impairment that was only present when they were febrile. The non-febrile patients had only mild if any hearing impairment. Electrophysiological tests revealed auditory neuropathy. Mapping with microsatellite markers revealed a compatible linkage in the DFNB9/OTOF region in the family, prompting us to run a molecular analysis of the 48 exons and of the OTOF intron-exon boundaries. This study revealed a novel mutation p.Glu1804del in exon 44 of OTOF. The mutation was found to be homozygous in the three patients and segregated with the hearing impairment within the family. The deletion affects an amino acid that is conserved in mammalian otoferlin sequences and located in the calcium-binding domain C2F of the protein.
AP-HP, Service de Génétique Clinique, Hôpital Armand-Trousseau, Paris, France.
Sandrine
S
Marlin
Delphine
D
Feldmann
Yann
Y
Nguyen
Isabelle
I
Rouillon
Natalie
N
Loundon
Laurence
L
Jonard
Crystel
C
Bonnet
Remy
R
Couderc
Eréa Noel
EN
Garabedian
Christine
C
Petit
Françoise
F
Denoyelle
D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D005091:Exons; D016326:Extracellular Matrix Proteins; D005260:Female; D005334:Fever / Q000150:complications*; D006319:Hearing Loss, Sensorineural / Q000209:etiology / Q000235:genetics*; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation; D011506:Proteins / Q000235:genetics; D017384:Sequence Deletion
C110668:COCH protein, human; D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins; C118457:OTOF protein, human; D011506:Proteins