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Übersichtsarbeit

Zur Genetik der Lese-Rechtschreibschwäche

Published Online:https://doi.org/10.1024/1422-4917.34.6.435

Zusammenfassung: Die Lese-Rechtschreibstörung (LRS) ist eine der häufigsten Entwicklungsstörungen. Die Ursachen dieser komplexen Störung sind bisher nur kaum verstanden. Familienuntersuchungen zeigen, dass die LRS familiär gehäuft auftritt und dass das Risiko für ein Geschwisterkind, eine LRS zu entwickeln, ca. 3,5fach erhöht ist. Verschiedene kognitive Fähigkeiten sind mit der LRS korreliert. Hierzu gehören die phonologische Bewusstheit, orthographisches Wissen, phonologisches Dekodieren, auditives Kurzzeitgedächtnis und schnelles Benennen. Eine familiäre Häufung dieser mit der LRS korrelierten Dimensionen und eine hohe Erblichkeit (Heritabilität) wurden wiederholt gefunden. Die Heritabilität für die Lesefähigkeit liegt zwischen 50-60%, für die Rechtschreibstörung zwischen 50 und 70%. Durch genomweite Kopplungsuntersuchungen wurden bisher 9 Kandidatengenregionen (DYX1-9) identifiziert. Vier Kandidatengene, DCDC2, KIAA0319, ROBO1 und DYX1C1 wurden kürzlich beschrieben. Diese beeinflussen die neuronale Migration und sind daher funktionell aussichtsreiche Kandidatengene für die LRS. Allerdings konnte bisher keine funktionell relevante Mutation gefunden werden. Die Komorbidität zwischen LRS und ADHD sowie LRS und Sprachentwicklungsstörungen könnte zum Teil durch gemeinsame genetische Faktoren erklärt werden. In der Zukunft wird es für die Ursachenforschung der LRS entscheidend sein, möglichst alle ursachenrelevanten Dimensionen gemeinsam an ausreichend großen Stichproben zu untersuchen. Neben den relevanten neurobiologischen Faktoren sollten auch Umweltfaktoren und die verschiedenen Interaktionen, wie z.B. Gen-Umwelt und Gen-Gen-Interaktionen untersucht werden. In einem europäischen, kollaborativen Forschungsvorhaben (NeuroDys) wird weltweit die größte Stichprobe von Kindern mit einer LRS gesammelt und untersucht, um durch ein verbessertes Ursachenverständnis unter Einschluss der Identifikation von genetischen Risikofaktoren die Komplexität des Störungsbildes besser zu verstehen und perspektivisch spezifische Therapien zu entwickeln.


Genetics of dyslexia

Summary: Dyslexia is a very common developmental disorder. The aetiology of this complex disorder must in large part still be clarified. Dyslexia segregates in families and the risk for a sibling to become dyslexic is 3.5-fold increased. Different phenotypic dimensions are correlated with dyslexia. These are mainly phonological awareness, phonological decoding, orthographic coding, auditory short-term memory, and rapid naming. The correlated dimensions segregate in families and were found to be heritable. The heritability of word reading lies between 50% and 60%, and that of spelling between 50% and 70%. Based on genome wide linkage analyses, nine candidate gene regions (DYX1-DYX9) could be identified. Recently, four candidate genes, DCDC2, KIAA0319, ROBO1 and DYX1C1 were identified by systematic association analyses. All these genes play a function role in neuronal migration, making them promising candidate genes for dyslexia. However, a functionally relevant mutation has not yet been identified. The comorbidity between dyslexia and ADHD and between dyslexia and SLI could be explained, at least in part, by genetic factors. For future research, all relevant factors playing a functional role in dyslexia should be investigated in sufficiently large samples. This research should integrate genetic, neurobiological, and environmental factors. For an understanding of causes, it is very helpful to understand the interaction between different factors, namely gene-environmental and gene-gene interaction. In a recent project funded by the EU in the Sixth Framework (www.neurodys.com), the worldwide largest sample of children with dyslexia will be sampled and investigated. The goal of this project is to investigate the biological basis of dyslexia in order to improve the basis for the development of successful diagnostics and therapies.

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