Developmental Dyslexia (DD) is a neurodevelopmental disorder affecting reading skills¹^,². Human studies have provided insights into its genetic basis^2,3 supported by animal studies providing evidence about the role of candidate genes in neural migration and axonal growth⁴. While children with DD exhibit structural connectivity differences⁵^,⁶, the genetic factors underlying these variations remain unclear⁶. This study explores the impact of the READ1 deletion (READ1d) on structural connectivity, building on prior findings linking this gene to white matter changes⁷.

Using anatomically constrained spherical deconvolution tractography⁸, we analyzed white matter connectivity in 75 children: 19 DD without READ1d, 22 DD with READ1d, 22 typical readers (TR) without READ1d, and 17 TR with READ1d. A 90-node brain atlas⁹ defined the connectivity graph, from which global (global efficiency, network local efficiency, clustering coefficient, small-worldness) and local network metrics (nodal degree, nodal local efficiency, betweenness centrality) were extracted¹⁰.

A generalized linear model investigated the effects of READ1d, reading proficiency and their interaction on structural connectivity, controlling for sex, age, IQ, and DSMinattention. Regardless of reading proficiency, children with READ1d exhibited significantly lower global efficiency (p<0.05) compared to those without READ1d, indicating reduced network integration. Additionally, they showed lower nodal degree (p<0.001) in the left medial orbital frontal, bilateral superior temporal, and right transverse temporal regions, aligning with reduced fractional anisotropy in the bilateral temporal areas⁷. These findings underscore READ1d’s role in shaping structural connectivity in DD-related regions, emphasizing the need for further research integrating genetics, neuroimaging, and cognition. References

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