title: Clinical aspects of an autosomal dominantly inherited hearing impairment linked to the DFNA60 locus on chromosome 2q23.1-2q23.3.
abstract: A total of 64 loci for autosomal dominant non-syndromic hearing impairment have been described, and the causative genes have been identified for 24 of these. The present study reports on the clinical characteristics of an autosomal dominantly inherited hearing impairment that is linked to a region within the DFNA60 locus located on chromosome 2 in q22.1-24.1. A pedigree spanning four generations was established with 13 affected individuals. Linkage analysis demonstrated that the locus extended over a 2.96 Mb region flanked by markers D2S2335 and D2S2275. The audiograms mainly showed a distinctive U-shaped configuration. Deterioration of hearing started at a wide age range, from 12 to 40 years. Cross-sectional analysis showed rapid progression of hearing impairment from mild to severe, between the ages of 40 and 60 years, a phenomenon that is also observed in DFNA9 patients. The results of the individual longitudinal analyses were generally in line with those obtained by the cross-sectional analysis. Speech recognition scores related to the level of hearing impairment (PTA1,2,4 kHz) appeared to be fairly similar to those of presbyacusis patients. It is speculated that hearing impairment starting in mid-life, as shown by DFNA60 patients, could play a role in the development of presbyacusis. Furthermore, speech recognition did not deteriorate appreciably before the sixth decade of life. We conclude that DFNA60 should be considered in hearing impaired patients who undergo a rapid progression in middle age and are negative for DFNA9. Furthermore, cochlear implantation resulted in good rehabilitation in two DFNA60 patients.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. E.vanBeelen@kno.umcn.nl
authors.forename: E
authors.initials: E
authors.lastname: van Beelen
authors.forename: M
authors.initials: M
authors.lastname: Schraders
authors.forename: P L M
authors.initials: PL
authors.lastname: Huygen
authors.forename: J
authors.initials: J
authors.lastname: Oostrik
authors.forename: R F
authors.initials: RF
authors.lastname: Plantinga
authors.forename: W
authors.initials: W
authors.lastname: van Drunen
authors.forename: R W J
authors.initials: RW
authors.lastname: Collin
authors.forename: D P
authors.initials: DP
authors.lastname: Kooper
authors.forename: R J E
authors.initials: RJ
authors.lastname: Pennings
authors.forename: C W R J
authors.initials: CW
authors.lastname: Cremers
authors.forename: H
authors.initials: H
authors.lastname: Kremer
authors.forename: H P M
authors.initials: HP
authors.lastname: Kunst
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001301:Audiometry, Pure-Tone; D001302:Audiometry, Speech; D001307:Auditory Perception / Q000235:genetics*; D002648:Child; D002889:Chromosomes, Human, Pair 2; D019929:Cochlear Implantation; D018450:Disease Progression; D005260:Female; D005799:Genes, Dominant; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006309:Hearing / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology / Q000534:rehabilitation; D040941:Heredity; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D021641:Recognition, Psychology; D012720:Severity of Illness Index; D013065:Speech Intelligibility; D013067:Speech Perception; D055815:Young Adult