Brain Migration Disorder and T-Cell Activation Deficiency Associated with Abnormal Signaling through TCR/CD3 Complex and Hyperactivity of Fyn Tyrosine Kinase[*]

In this study we report on a patient affected by a brain migration disorder and a T-cell activation deficiency presumably inherited as an autosomal recessive trait.

The immunological evaluation revealed that the mitogen stimulation failed to induce a proper up-regulation of membrane expression of T-cell activation markers, and cell proliferation. This functional impairment was associated with abnormalities of the signal transduction process that follows T-cell receptor stimulation. A constitutive hyperphosphorylation of the Fyn tyrosine kinase was documented.

This is the first report on a T-cell signaling abnormality associated with a developmental brain disorder. Whether the alteration of Fyn, which plays a role in both neurological and immunological systems, is responsible for either disorder remains to be elucidated.

Key words

Brain migration disorder - T-cell immunodeficiency - Signal transduction - Fyn tyrosine kinase

1 Financial support: This work was supported by “Progetto MURST-PRIN” (Research Program of National Relevance) 1999, and by Biomed 2 # CT98-3007.

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1 Financial support: This work was supported by “Progetto MURST-PRIN” (Research Program of National Relevance) 1999, and by Biomed 2 # CT98-3007.