title: Audiometric characterization of a family with digenic autosomal, dominant, progressive sensorineural hearing loss.
abstract: In this study, a non-syndromic progressive bilateral high frequency hearing loss is described in a family with 141 identified members. Recent genetic analyses indicated a digenic inheritance with linkage to the gene loci DFNA2 and DFNA12. The affected family members who shared haplotypes at both loci (type I) showed an early postlingual onset and a more rapid rate of progress compared with those with one either of the two disease associated haplotypes (type II). The audiometric pattern was cochlear without a vestibular involvement. Auditory brainstem response audiometry and magnetic resonance imaging indicated normal retrocochlear features. The otoacoustic emissions were affected for both type I and type II, whereas the acoustic stapedius reflex thresholds were normal in most cases. It is concluded that both types had an outer hair cell/micro-mechanical abnormality, but that the DFNA 2 type might have an additional dysfunction at the level of the inner hair cells. It is furthermore pointed out that the application of refined audiometric techniques as well as a further development of new techniques is needed in order to characterize the phenotypes of the rapidly expanding number of genetically defined inner ear abnormalities.
authors.affiliation: Ahlsén Research Institute, Orebro Medical Centre Hospital, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Borg
authors.forename: E
authors.initials: E
authors.lastname: Samuelsson
authors.forename: N
authors.initials: N
authors.lastname: Dahl
mesh_terms: D000328:Adult; D000368:Aged; D001301:Audiometry, Pure-Tone / Q000379:methods; D001309:Auditory Threshold / Q000502:physiology; D001696:Biomechanical Phenomena; D018450:Disease Progression; D007758:Ear, Inner / Q000002:abnormalities; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005260:Female; D008040:Genetic Linkage; D006198:Hair Cells, Auditory / Q000503:physiopathology; D006239:Haplotypes / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012022:Reflex, Acoustic / Q000502:physiology; D013198:Stapedius / Q000502:physiology