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Laryngorhinootologie 2020; 99(12): 853-862
DOI: 10.1055/a-1190-4173
Übersicht

Molekulare und funktionale Abklärung hereditärer Schwerhörigkeiten am Beispiel des SLC26A4-Gens

Molecular and functional testing in case of hereditary hearing loss associated with the SLC26A4 gene
Sebastian Roesch
1   Universitätsklinik für Hals-Nasen-Ohrenkrankheiten der Paracelsus Medizinischen Privatuniversität Salzburg, SALK, Salzburg, Austria
,
Emanuele Bernardinelli
2   Universitätsinstitut für Pharmakologie und Toxikologie der Paracelsus Medizinischen Privatuniversität Salzburg, Austria
,
Saskia Wortmann
3   Universitätsklinik für Kinder- und Jugendheilkunde der Paracelsus Medizinischen Privatuniversität Salzburg, SALK, Salzburg, Austria
,
Johannes A. Mayr
3   Universitätsklinik für Kinder- und Jugendheilkunde der Paracelsus Medizinischen Privatuniversität Salzburg, SALK, Salzburg, Austria
,
Ingrid Bader
4   Division für klinische Genetik, Universitätsklinik für Kinder- und Jugendheilkunde der Paracelsus Medizinischen Privatuniversität Salzburg, SALK, Salzburg, Austria
,
Gregor Schweighofer-Zwink
5   Universitätsklinik für Nuklearmedizin und Endokrinologie der Paracelsus Medizinischen Privatuniversität Salzburg, SALK, Salzburg, Austria
,
Gerd Rasp
1   Universitätsklinik für Hals-Nasen-Ohrenkrankheiten der Paracelsus Medizinischen Privatuniversität Salzburg, SALK, Salzburg, Austria
,
Silvia Dossena
2   Universitätsinstitut für Pharmakologie und Toxikologie der Paracelsus Medizinischen Privatuniversität Salzburg, Austria
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Zusammenfassung

Die in den vergangenen Jahren zunehmende Verfügbarkeit molekularer Untersuchungstechniken führt zu einer steigenden Anzahl diagnostizierter genetischer Varianten im Genom untersuchter Patienten. Am Beispiel der hereditären Innenohrschwerhörigkeit wird bei Betrachtung der Vielzahl publizierter Berichte über die mögliche Beteiligung einzelner Gene an der Pathogenese deutlich, welche Herausforderungen die Zunahme molekularer Informationen für die Interpretation mit sich bringt.

In dieser Übersichtsarbeit werden anhand des Beispiels des SLC26A4-Gens und den damit verbundenen Formen einer hereditären Innenohrschwerhörigkeit die derzeit vorhandenen Möglichkeiten einer systematischen Abklärung und Interpretation dargestellt. Neben einer Beschreibung der physiologischen Funktion des resultierenden Pendrin-Proteins werden molekulare Untersuchungsmöglichkeiten zur Beurteilung der Funktion im Fall von nachgewiesenen Genvarianten erläutert. Die im Rahmen eines primär wissenschaftlichen Ansatzes resultierenden Ergebnisse auf molekularer Ebene dienen im klinischen Alltag der Interpretation hinsichtlich des kausalen Zusammenhangs zwischen einer nachgewiesenen Genvariante (Genotyp) und der Innenohrschwerhörigkeit (Phänotyp). Schließlich wird auf die mögliche Notwendigkeit einer weiteren interdisziplinären Abklärung, z. B. mithilfe einer Perchlorat-Testung der Schilddrüse, sowie therapeutische Möglichkeiten eingegangen.

Abstract

Due to development of molecular techniques at hand, the number of genomic sequence variants detected in patient investigations is rising constantly. The number of potentially involved genes in hereditary hearing loss is rising simultaneously.

In this overview, current methods for diagnostic workup on a molecular and functional level for variants of the SLC26A4 gene are described. Based on the description of the physiological function of the resulting protein Pendrin, molecular investigations for interpretation of the function are explained. Based on these investigations, the potential clinical consequences of a variant may be predicted more precisely and simplify routine reporting of a proven genotype and a phenotype, at hand. Finally, subsequent clinical investigations necessary, such as perchlorate discharge test, as well as therapeutic options are discussed.

Schlüsselwörter

Pendrin - erweiterter vestibulärer Aquädukt - EVA - Pendred-Syndrom - angeborene Innenohrschwerhörigkeit - funktionale Diagnostik - DFNB4 - SLC26A4

Key words

pendrin - enlarged vestibular aqueduct - Pendred syndrome - hereditary hearing loss - functional testing


Publication History

Received: 01 August 2019

Accepted: 26 May 2020

Article published online:
11 December 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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