title: Two families with phenotypically different hereditary low frequency hearing impairment: longitudinal data and linkage analysis.
abstract: Two families with low frequency hearing impairment have been described previously. Family A (Danish) presented a sensorineural hearing impairment most pronounced for frequencies below 2 kHz and a pedigree typical for an autosomal dominant trait with complete penetrance (Königsmark type). Family B, originating from the Faroe Islands, showed conflicting audiological test results, making a valid classification impossible. The pedigree suggested autosomal dominant inheritance with incomplete penetrance. The objectives of the present study are to acquire longitudinal audiometric data, to clarify the mode of transmission, and to localize the mutant gene by reevaluation of the two families. The methods used are evaluation of the family history, audiological examination and linkage analysis. In family A, update of the pedigree fitted the assumption of an autosomal dominant mode of transmission. In six examined subjects audiological data were available from the previous study. The median progression over a 13-21-year period was 13.8 dB HL for the thresholds, averaged across 0.5, 1, 2 and 4 kHz and 17.5 dB HL for the thresholds, averaged across 2 and 4kHz. In family B, the probable mode of transmission is autosomal dominant with reduced penetrance. In this family no progression of the hearing impairment was found. Linkage analysis of family A showed a lod score of 3.53, indicating significant linkage to the loci DFNA6 and DFNA14 on chromosome 4, previously found to be involved in low frequency hearing impairment. Family B was not linked to the region on chromosome 4, further adding to the genetic heterogeneity in low frequency sensorineural hearing impairment.
authors.affiliation: Department of Audiology, Copenhagen University Hospital Bispebjerg, Denmark. mbille@dadlnet.dk
authors.forename: M
authors.initials: M
authors.lastname: Bille
authors.forename: L
authors.initials: L
authors.lastname: Munk-Nielsen
authors.forename: L
authors.initials: L
authors.lastname: Tranebjaerg
authors.forename: A
authors.initials: A
authors.lastname: Parving
mesh_terms: D000328:Adult; D001301:Audiometry, Pure-Tone; D005260:Female; D005500:Follow-Up Studies; D008040:Genetic Linkage; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D012720:Severity of Illness Index; D013069:Speech Reception Threshold Test