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Data from: Abnormal brain development in child and adolescent carriers of mutant huntingtin

Cite this dataset

van der Plas, Ellen et al. (2019). Data from: Abnormal brain development in child and adolescent carriers of mutant huntingtin [Dataset]. Dryad.


Objective: The huntingtin gene is critical for the formation and differentiation of the central nervous system, which raises questions about the neurodevelopmental impact of CAG expansion mutations within this gene (mHTT) that cause Huntington’s Disease (HD). We sought to determine if child and adolescent carriers of mHTT exhibit different brain growth compared to peers without the mutation. To test this hypothesis, we conducted structural magnetic resonance imaging in children and adolescents who are at risk for HD. We also explored whether variation in the length of CAG expansion affects brain development. Methods: Children and adolescents (age 6 – 18) with a parent or grandparent diagnosed with HD underwent neuroimaging and blinded genetic testing to confirm the presence or absence of mHTT. Seventy-five individuals were Gene-Expanded (GE) and 97 individuals were Gene-Non-Expanded (GNE). The GE group was estimated to be on average 35 years from clinical onset. Following an accelerated longitudinal design, age-related change in brain regions were estimated. Results: Age-related striatal volume changes differed significantly between the GE and GNE groups, with initial hypertrophy and more rapid volume decline in GE. This pattern was exaggerated with CAG expansion length for CAG > 50. A similar age-dependent group difference was observed for the globus pallidus, but not in other major regions. Conclusions: Our results suggest that pathogenesis of HD begins with abnormal brain development, which sets the stage for different trajectories of striatal growth and development. An understanding of potential neurodevelopmental features associated with mHTT may be needed for optimized implementation of preventative gene silencing therapies, such that normal aspects of neurodevelopment are preserved as neurodegeneration is forestalled.

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