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Der Ophthalmologe

, Volume 104, Issue 6, pp 490–498 | Cite as

Genetische und klinische Heterogenität bei LCA-Patienten

Das Ende der Einheitlichkeit
  • M.N. Preising
  • K. Paunescu
  • C. Friedburg
  • B. Lorenz
Originalien

Zusammenfassung

Hintergrund

Die Diagnose kongenitale Lebersche Amaurose (LCA) umfasst Patienten mit frühkindlicher Netzhautdystrophie und früher Erblindung.

Methoden

In einer Fallserie mit 135 Familien mit schwerer frühkindlicher Netzhautdystrophie wurde die übliche ophthalmologische Untersuchung um eine Zweifarbenschwellenperimetrie, eine Fundusautofluoreszenz (FAF) und eine optische Kohärenztomographie (OCT) erweitert. Eine molekulargenetische Untersuchung von AIPL1, CRB1, CRX, GUCY2D, LRAT, RPE65, RPGRIP und TULP1 schloss sich an.

Ergebnisse

GUCY2D-Mutationen erzeugten bei unauffälligem Fundus den schwersten Phänotyp. Bei RPE65-Mutationen konnte trotz unauffälliger Funduskopie keine FAF nachgewiesen werden. CRB1-Mutationen zeigten im OCT eine Verdickung der Neuroretina. CRX-Mutationen korrelierten mit einer progressiven Zapfen-Stäbchen-Dystrophie.

Schlussfolgerung

Eine Genotyp-Phänotyp-Korrelation für ausgewählte Gene erlaubt eine optimierte Strategie für die molekulargenetische Untersuchung.

Schlüsselwörter

Kongenitale Lebersche Amaurose Genotyp-Phänotyp-Korrelation Frühkindliche schwere Netzhautdystrophie Genetische Heterogenität Klinische Heterogenität 

Genetic and clinical heterogeneity in LCA patients

The end of uniformity

Abstract

Background

Leber congenital amaurosis (LCA) usually describes patients with severely reduced vision due to a retinal dystrophy in early childhood.

Methods

In 135 families in a case series with severely reduced vision due to a retinal dystrophy in early childhood a complete ophthalmologic examination was extended by two-color threshold perimetry, fundus autofluorescence (FAF), und optical coherence tomography (OCT). Mutation screening included AIPL1, CRB1, CRX, GUCY2D, LRAT, RPE65, RPGRIP, and TULP1.

Results

GUCY2D mutations caused the most severe phenotype with severely reduced vision from birth but unremarkable fundus appearance. RPE65 mutations were correlated with an obvious lack of FAF. CRB1 mutations showed a significantly thickened retina on OCT. CRX mutations were associated with a progressive form of cone-rod dystrophy.

Conclusion

A genotype-phenotype correlation for selected genes allows an optimized strategy for the molecular genetic work-up.

Keywords

Leber congenital amaurosis Genotype-phenotype correlation Early-onset severe retinal dystrophy Genetic heterogeneity Clinical heterogeneity 

Notes

Danksagung

Wir danken den Familien und Patienten für ihre Kooperation und Geduld bei den Untersuchungen. Ebenso gilt unser Dank Prof. U. Kellner, Prof. G. Kommerell und Prof. K. Rüther für die Überweisung von Patienten. Frau U. Brauer, Frau D. Glatz und Frau R. Foeckler haben exzellente Arbeit bei der Genotypisierung geleistet. Dem Geschick und der Geduld von Frau U. Biendl und Frau B. Langer ist es zu verdanken, dass die nicht immer einfachen elektrophysiologischen und psychophysischen Untersuchungen verwertbare Ergebnisse lieferten.

Für die finanzielle Unterstützung des Projekts bedanken wir uns bei der Deutschen Forschungsgemeinschaft (DFG Lo457/3, Lo457/5), der Pro Retina Deutschland e.V. und der Regensburger Forschungsförderung in der Medizin (ReForM).

Interessenkonflikt

Es besteht kein Interessenkonflikt. Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen. Die Präsentation des Themas ist unabhängig und die Darstellung der Inhalte produktneutral.

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Copyright information

© Springer Medizin Verlag 2007

Authors and Affiliations

  • M.N. Preising
    • 1
  • K. Paunescu
    • 1
  • C. Friedburg
    • 1
  • B. Lorenz
    • 1
  1. 1.Abt. für Kinderophthalmologie, Strabismologie und OphthalmogenetikKlinikum der Universität RegensburgRegensburgDeutschland

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