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DOI: 10.1055/s-2005-870302
Pseudodominanz zweier rezessiver Connexin-Mutationen bei nicht-syndromaler Hörstörung?
Pseudodominants of Two Recessive Connexin Mutations in Non-syndromic Sensorineural Hearing Loss?Publikationsverlauf
Eingegangen: 20. September 2004
Angenommen: 27. Juni 2005
Publikationsdatum:
12. September 2005 (online)
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Zusammenfassung
Hintergrund: Bisher wurden mehr als 100 Genorte identifiziert, die mit Erkrankungen des Innenohrs in Verbindung gebracht werden. Genetische Defekte im Connexin-26-Gen (GJB2) sind in etwa der Hälfte aller Fälle die häufigste Ursache für nicht-syndromale Innenohrschwerhörigkeit. Die Connexin-26- und -30-Gene (GJB2 und GJB6) sind auf Chromosom 13q11-12 benachbart lokalisiert. Im Innenohr wurden bisher vier verschiedene Connexinmoleküle nachgewiesen. Connexine gehören zu der Gruppe von „Gap Junction”-Proteinen, die Connexone ausbilden. Diese bestehen aus sechs Connexinmolekülen. Sie sind für den Austausch von Ionen und kleineren Molekülen zwischen benachbarten Zellen verantwortlich. Methode: Der Nachweis der Mutationen in den Connexin-Genen 26, 30, und 31 (GJB2, GJB3, and GJB6) erfolgte durch direkte Sequenzierung der kodierenden Exone einschließlich der Intronübergänge. Ergebnis: In den beteiligten Familien konnten erstmals drei heterozygote Mutationen in den Connexin-26- und -30-Genen nachgewiesen werden, die in Kombination, 35ΔG mit 146/147ΔC und 35ΔG mit GJB6-D13S1830, bei den betroffenen Patienten zu einer nicht syndromalen Taubheit führten. Schlussfolgerung: Bei Hinweisen auf familiäre Hörstörungen ist es empfehlenswert, in Ergänzung zu einer spezifischen Hördiagnostik eine Mutationsanalyse der Connexin-Gene (GJB2, GJB3 & GJB6) durchzuführen, um rechtzeitig eine optimale und qualifizierte Förderung der Sprachentwicklung durch Hörhilfen, bis hin zur CI-Implantation, einzuleiten.
Abstract
Background: Hitherto more than hundred genes and gene loci for non-syndromic or syndromic deafness have been identified. Mutations in the connexin 26 gene (GJB2) account for up to 50 % of the cases of autosomal recessive hearing loss. The genes GJB2 (Connexin 26), GJB3 (connexin 31) and GJB6 (connexin 31) are located on chromosome 13q11-12. In the inner ear up to four different connexins are expressed. Connexins appertain to a group of gap junction proteins. These proteins can oligomerize to form single-membrane channels called connexons. Each connexon is composed of six subunits, that allow communication between adjacent cells by providing a channel for diffusion of ions, metabolites and second messengers. Method: Each of the exons and flanking splice regions of the connexin 26, 30, and 31 genes (GJB2, GJB3, and GJB6) have been analysed by direct sequencing. Results: In the involved families three heterozygous mutations could be detected in the connexin 26 (GJB2) and connexin 30 (GJB6) genes. If a combination of two of those mutations occurs, 35ΔG with 146/147ΔC and 35ΔG with GJB6-D13S1830 it results in hearing loss and deafness. Conclusion: By evidences of a familial background of hearing loss it is reasonable to analyse the connexin genes (GJB2, GJB3 & GJB6) for mutations, additionally to a specific hearing diagnostic, in order to enhance linguistic development through hearing aid or CI-implantation at an early stage.
Schlüsselwörter
Nicht-syndromale Innenohrschwerhörigkeit - Taubheit - Connexin 26 (GJB2) - Connexin 31 (GJB3) - Connexin 30 (GJB6) - Mutationsanalyse
Key words
Non-syndromic hearing loss - deafness - Connexin 26 (GJB2) - Connexin 31 (GJB3) - Connexin 30 (GJB6) - mutationsanalysis
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Dr. Ralf Birkenhäger
Universitätsklinik für Hals-, Nasen- und Ohrenheilkunde und Poliklinik
Universitätsklinikum Freiburg · Killianstraße 5 · D-79106 Freiburg
eMail: birkenhaeger@hno.ukl.uni-freiburg.de