The c-actin gene (ACTG1) encodes a major cytoskeletal protein of the sensory hair cells of the cochlea. Recently, mutations in ACTG1 were found to cause autosomal dominant, progressive, sensorineural hearing impairment linked to the DFNA20/26 locus on chromosome 17q25.3 in four American families and in one Dutch family. We report here the linkage of autosomal dominant, progressive, sensorineural hearing impairment in a large Norwegian family to the DFNA20/26 locus. Sequencing of ACTG1 identified a novel missense mutation (c.1109T4C; p.V370A) segregating with the hearing loss. Functional analysis in yeast showed that the p.V370A mutation restricts cell growth at elevated temperature or under hyperosmolar stress. Molecular modelling suggested that the p.V370A mutation modestly alters a site for protein -protein interaction in c-actin and thereby modestly alters c-actin-based cytoskeletal structures. Nineteen Norwegian and Danish families with autosomal, dominant hearing impairment were analyzed for mutations in ACTG1 by sequencing, but no disease-associated mutations were identified. Finally, a longterm follow-up of the hearing loss progression associated with the p.V370A mutation in ACTG1 is provided. The present study expands our understanding of the genotype -phenotype relationship of this deafness gene and provides a sensitive and simple functional assay for missense mutations in this gene, which may assist future molecular diagnosis of autosomal-dominant hearing impairment. Finally, the present results do not indicate that mutations in ACTG1 are a frequent cause of autosomal-dominant postlingual sensorineural hearing impairment in Norway nor Denmark.
The muscles from seven human larynxes removed by laryngectomy have been examined for actomyosin ATPase by histochemical methods. The various muscles contained a mixture of ATPase low (type I) and ATPase high (type II) muscle fibres. The thyreoarytenoid muscle had the highest proportion of type II fibres (65%) and the posterior cricoarytenoid muscle had the highest proportion of type I fibres (67%). The other laryngeal muscles had intermediate valves. All human laryngeal muscles had a higher percetage of type I fibres than the corresponding muscles in animals so far examined, a finding which may be related to the development of speech.
Introduction: An important question, which confronts every otosclerosis surgeon, is which type of stapes prosthesis should be chosen. A wide variety of prostheses with different shapes, material and shaft diameters is commercially available. This paper addresses the importance of the piston shaft diameter. Patients and Material: In this retrospective study of 225 consecutive stapedotomies performed in the period 1981–1998, prostheses with a diameter of 0.4, 0.6 and 0.8 mm have been compared. Results: Bigger pistons give better hearing results for frequencies up to and including 2 kHz.
Hereditary hearing impairment affects about 1 in 1000 newborns. In most cases hearing loss is non-syndromic with no other clinical features, while in other families deafness is associated with specific clinical abnormalities. Analysis of large families with non-syndromic and syndromic deafness have been used to identify genes or gene locations that cause hearing impairment. The present report describes a large Norwegian family with autosomal dominant non-syndromic, progressive high tone hearing loss with linkage to 1q21-q23. A maximum LOD score of 7.65 (theta = 0.00) was obtained with the microsatellite marker D1S196. Analysis of recombinant individuals maps the deafness gene (DFNA7) to a 22 cM region between D1S104 and D1S466. The region contains several attractive candidate genes. This report supports the idea of extensive genetic heterogeneity in hereditary hearing impairment and represents the first localization of a deafness gene in a Norwegian family.
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