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Genetik des Usher-Syndroms

Genetics of Usher syndrome

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Zusammenfassung

Seit der Identifizierung des ersten Usher-Gens (MYO7A) vor 14 Jahren hat die Erforschung der genetischen Grundlagen dieser Erkrankung enorme Fortschritte gemacht. Bemerkenswert ist die ausgeprägte nichtallelische genetische Heterogenität mit zurzeit 9 bekannten Genen. Die meisten der von den Usher-Genen kodierten Proteine haben ähnliche Funktionen, befinden sich in den gleichen Regionen von Innenohrhaarzellen und retinalen Photorezeptoren und interagieren miteinander. Etwa 80% der Patienten haben Mutationen in einem der bekannten Gene. Eine Herausforderung der genetischen Grundlagenforschung ist es, die verbleibenden Gene zu finden. Weitgehend unklar ist auch noch, welche genetischen Faktoren die mitunter ausgeprägte klinische Variabilität, die auch zwischen betroffenen Geschwistern beobachtet werden kann, bedingen. Eine umfassende molekulare Routinediagnostik für alle Usher-Gene wird durch die Etablierung neuer Hochdurchsatzverfahren angestrebt und ist wünschenswert: Die frühe molekulargenetische Sicherung der Diagnose (bzw. ihr Ausschluss) ist für das klinische Management und die Lebensplanung von großer Bedeutung, da so geklärt werden könnte, ob der angeborenen Hörstörung im weiteren Leben eine Netzhauterkrankung folgt.

Abstract

Since the first gene (MYO7A) for Usher syndrome was identified 14 years ago, there has been substantial progress in the elucidation of the genetic basis of this disorder, revealing extensive genetic heterogeneity (with nine genes known to date). Most Usher genes have similar functions, localize to similar regions in inner ear hair cells and retinal photoreceptors, and interact with each other. Approximately 80% of the patients carry mutations in one of the known Usher genes. One major challenge for the scientific community is to identify the remaining causative genes. Moreover, it is still largely unclear which genetic factors are responsible for the clinical variability that can be observed even between affected siblings. The establishment of high-throughput techniques shall soon provide comprehensive genetic testing covering all genes, which would be desirable: Early confirmation (or exclusion) of the diagnosis would be important for the individual patient, as it could help predict whether retinal degeneration can be expected in addition to the congenital hearing impairment.

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Abbreviations

arRP:

Autosomal-rezessive Retinitis pigmentosa

AS:

Außensegment

IS:

Innensegment

NSHL:

„Non-syndromic hearing loss“

RP:

Retinitis pigmentosa

S:

Synapse

USH1, USH2:

Usher-Syndrom Typ 1 bzw. Typ 2

VZ:

Verbindendes Zilium

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  1. Institut für Humangenetik, Universitätsklinikum Köln, Kerpener Straße 34, 50931, Köln, Deutschland

    H.J. Bolz

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  1. H.J. Bolz
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Correspondence to H.J. Bolz.

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Mit Unterstützung der DFG (BO2954/1-2) und Forschung Contra Blindheit – Initiative Usher-Syndrom e.V.

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Bolz, H. Genetik des Usher-Syndroms. Ophthalmologe 106, 496–504 (2009). https://doi.org/10.1007/s00347-008-1887-8

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