A genotype-phenotype correlation with gender-effect for hearing impairment caused by TECTA mutations.
| Autor: | Pfister M; Department of Otolaryngology, University of Tübingen, Germany., Thiele H, Van Camp G, Fransen E, Apaydin F, Aydin O, Leistenschneider P, Devoto M, Zenner HP, Blin N, Nürnberg P, Ozkarakas H, Kupka S |
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| Jazyk: | angličtina |
| Zdroj: | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology [Cell Physiol Biochem] 2004; Vol. 14 (4-6), pp. 369-76. |
| DOI: | 10.1159/000080347 |
| Abstrakt: | Background: Alpha-tectorin is a noncollagenous component of the tectorial membrane which plays an essential role in auditory transduction. In several DFNA12 families mutations in TECTA, the gene encoding alpha-tectorin, were shown to cause hearing impairment (HI) with different phenotypes depending on the location of the mutation. Methods/results: Here we report a Turkish family displaying autosomal dominant inherited HI. Linkage analysis revealed significant cosegregation (LOD score: 4.6) of the disease to markers on chromosome 11q23.3- q24. This region contains the TECTA gene which was subsequently sequenced. A nucleotide change in exon 13, 4526T>G, was detected leading to a substitution from cysteine to glycine at codon 1509 of the TECTA protein. This cysteine is located in vWFD4 domain, a protein domain which is supposed to be involved in disulfide bonds and protein-protein interactions. Conclusions: It is conspicuous that the phenotype in this family correlates with other families, also displaying mutations involving conserved cysteines. In all three families these mutations result in progressive HI involving high frequencies. In contrast, mutations which are not affecting the vWFD domains seem to provoke mid-frequency sensorineural HI. Furthermore, evaluation of clinical data in our family revealed a gender effect for the severity of hearing impairment. Males were significantly more affected than females. The identification of the third family displaying a missense mutation in the vWFD domain of alpha-tectorin underlines the phenotype-genotype correlation based on different mutations in TECTA. (Copyright 2004 S. Karger AG, Basel) |
| Databáze: | MEDLINE |
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