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 re cessive trait. The immunological evaluation revealed that the mitogen stimulation failed t o 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 tyrosi ne 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 e ither disorder remains to be elucidated.