title: Sex-related hearing impairment in Wolfram syndrome patients identified by inactivating WFS1 mutations.
abstract: This study examined the audiovestibular profile of 11 Wolfram syndrome patients (4 males, 7 females) from 7 families, with identified WFS1 mutations, and the audiometric profile of 17 related heterozygous carriers of WFS1 mutations. Patients with Wolfram syndrome showed a downsloping audiogram and progressive hearing impairment. None of the carriers had sensorineural hearing loss. Two patients with missense (non-inactivating) mutations in WFS1 had normal hearing and mild symptoms of Wolfram syndrome and were excluded from the analyses. Of the identified patients with inactivating WFS1 mutations, 5 female patients were significantly more hearing impaired than four male patients (p < 0.05). Female patients showed hearing impairment progressing by 1.5-2.0 dB HL per year for the low frequencies and 4.0-4.5 dB HL per year for the mid and high frequencies. The age of onset (90% phoneme recognition score) was 21 years and the onset level 78 dB HL. The deterioration rate was 4.0% per year and the deterioration gradient 1.4% per dB HL. One of the 6 examined patients had vestibular areflexia.
authors.affiliation: Department of Otorhinolaryngology, UMC St. Radboud, Nijmegen, Belgium. r.pennings@kno.umcn.nl
authors.forename: Ronald J E
authors.initials: RJ
authors.lastname: Pennings
authors.forename: Patrick L M
authors.initials: PL
authors.lastname: Huygen
authors.forename: Jody M W
authors.initials: JM
authors.lastname: van den Ouweland
authors.forename: Kim
authors.initials: K
authors.lastname: Cryns
authors.forename: Lambert D
authors.initials: LD
authors.lastname: Dikkeschei
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
authors.forename: Cor W R J
authors.initials: CW
authors.lastname: Cremers
mesh_terms: D000328:Adult; D001301:Audiometry, Pure-Tone; D001309:Auditory Threshold; D003430:Cross-Sectional Studies; D005260:Female; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D012737:Sex Factors; D014929:Wolfram Syndrome / Q000150:complications* / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein