Zusammenfassung
Bis Mitte der 2000er-Jahre konnte Patienten mit Netzhautdystrophien nur in sehr eingeschränktem Maße eine molekulargenetische Diagnostik zur Diagnosesicherung und spezifischen humangenetischen Beratung angeboten werden. Viele der Gene, deren Mutationen z. B. zu Retinitis pigmentosa, Leberscher kongenitaler Amaurose und Zapfen-Stäbchen-Dystrophien führen, waren bereits bekannt, die verfügbaren Methoden der DNA-Sequenzanalyse aber für eine Routinediagnostik zu teuer und langwierig. Die unter „next-generation sequencing“ (NGS) zusammengefassten Verfahren der Hochdurchsatzsequenzierung haben dies grundlegend geändert: Zunächst in der Forschung angewendet, beschleunigten NGS-Verfahren die Identifizierung neuer Krankheitsgene erheblich – die Mutationen der meisten Patienten mit Netzhautdystrophien lassen sich heute bereits in den als krankheitsursächlich bekannten Genen finden. Seit etwa 2010 fand NGS Eingang in die Routinediagnostik. Dies gestattet bei den meisten Patienten eine genetische Diagnosestellung und somit eine spezifische genetische Beratung und medizinische Betreuung. Stetig verbesserte Bioinformatik und umfassende Datenbanken erleichtern die Auswertung der komplexen NGS-Daten. Eine intensive wissenschaftliche Vertrautheit mit der Genetik retinaler Dystrophien bleibt jedoch unabdingbar, um falsche Interpretationen der Daten zu vermeiden. Dies gilt auch für die enge Interaktion von Augenärzten und Humangenetikern.
Abstract
Until the mid-2000s, knowledge about the genetic causes of retinal dystrophies was not adequately translated into molecular diagnostics and genetic counselling offered to the patients. Although many genes whose mutations underlie retinal degeneration, e.g., retinitis pigmentosa, Leber congenital amaurosis and cone-rod dystrophies were known, they could not be analyzed on a routine diagnostic basis because DNA sequencing was too expensive and time-consuming. New methods summarized under the term next-generation sequencing (NGS) procedures for high-throughput sequencing have changed this completely. In its initial application in research NGS greatly accelerated the pace of novel disease gene identification: the mutations of most patients with retinal dystrophies can today be found in genes which are known to be associated with the condition. Since approximately 2010, NGS has expanded into routine diagnostics. In most patients, this now enables a genetic diagnosis and therefore specific genetic counselling and medical treatment. Constantly improving bioinformatics and comprehensive databases facilitate the evaluation of the complex NGS data. Nevertheless, profound scientific knowledge regarding the genetics of retinal dystrophies is indispensable to avoid erroneous data interpretation. This is also true for the close interaction between ophthalmologists and medical geneticists.
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Bolz, H.J. Genetische Diagnostik von Netzhautdystrophien. Ophthalmologe 115, 1028–1034 (2018). https://doi.org/10.1007/s00347-018-0762-5
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DOI: https://doi.org/10.1007/s00347-018-0762-5
Schlüsselwörter
- Next-generation sequencing
- Exomsequenzierung
- Genomsequenzierung
- Genotyp-Phänotyp-Korrelation
- Krankheitsgene