[Autoimmune lymphoproliferative syndrome: molecular diagnosis in two families].

Background And Objective: The autoimmune lymphoproliferative syndrome (ALPS) is a disorder caused by a defect in lymphocytes' apoptosis and characterized by non malignant lymphoproliferation, autoimmune features and increased TCR alpha + CD4CD8 cells. Most patients have a mutation in the TNFRSF6 gene, which encodes the Fas protein. Our aim was to identify mutations in this gene in two families with possible ALPS cases.

Patients And Method: Two patients with suspicion of ALPS, belonging to two unrelated families, were studied. To confirm such a diagnosis, immunoglobulin quantification, cellular phenotypic analysis by flow cytometry, IL-10 quantification, an apoptosis study, and molecular analysis were performed.

Results: Both patients showed hypergammaglobulinemia and an increased percentage of TCR alpha + CD4CD8 cells (family A patient: 14%; family B patient: 4.25%). In family A, in vitro Fas-mediated apoptosis was absent in the patient and markedly reduced in his father. In this family, both the patient and his father were heterozygous for the Fas mutation T1045C (Leu 268 Pro). The family B patient and her mother showed the Fas mutation G943T (Arg 234 Leu), both being heterozygous for it too. Both mutations are located in exon 9 of TNFRSF6 gene, affecting the death domain of the Fas protein.

Conclusions: The molecular study of these families confirms a diagnosis of ALPS and suggests that the causing defect of this syndrome is compatible with an autosomal dominant inheritance with incomplete penetrance.