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.
Del Giudice
E
E
Department of Pediatrics, Federico II University, Naples, Italy.
Gaetaniello
L
L
Matrecano
E
E
Cosentini
E
E
Ursini
M V
MV
Racioppi
L
L
Arrigo
G
G
Pignata
C
C
D020739:Brain Diseases, Metabolic, Inborn / Q000175:diagnosis / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D017252:CD3 Complex / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D002675:Child, Preschool; D004827:Epilepsy / Q000235:genetics; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008297:Male; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*
D017252:CD3 Complex; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn