RT Journal Article
T1 A homozygous Fas ligand gene mutation in a patient causes a new type of autoimmune lymphoproliferative syndrome
A1 Del-Rey, Manuel
A1 Bosque, Alberto
A1 Calleja, Sara
A1 Gomez-Rial, Jose
A1 Roldan, Ernesto
A1 Morales, Pablo
A1 Serrano, Antonio
A1 Anel, Alberto
A1 Ruiz Contreras, Jesús
A1 Paz Artal, Estela Natividad
A1 Allende Martínez, Luis Miguel
AB Autoimmune lymphoproliferative syndrome (ALPS) is characterized by lymphoproliferation and autoimmune clinical manifestations and is generally caused by defective Fas-mediated apoptosis. This report describes the first homozygous FASL gene mutation in a woman with clinical and immunologic features of ALPS. T-cell blasts from the patient did not induce FasL-mediated apoptosis on Fas-transfected murine L1210 or on Jurkat cells, and activation-induced cell death was impaired. Furthermore, Fas-dependent cytotoxicity was drastically reduced in COS cells transfected with the mutant FasL. In addition, FasL expression on T-cell blasts from the patient was similar to that observed in a healthy control, despite its bearing the high-producer genotype -844C/C in the FASL promoter. Sequencing of the patient's FASL gene revealed a new mutation in exon 4 (A247E). The location of A247E in the FasL extracellular domain and the conservation of the protein sequence of that region recorded in 8 species different from humans support the essential role of FasL COOH terminal domain in Fas/FasL binding. These findings provide evidence that inherited nonlethal FASL abnormalities cause an uncommon apoptosis defect producing lymphoproliferative disease, and they highlight the need for a review of the current ALPS classification to include a new ALPS type Ic subgroup.
PB American Society of Hematology
SN 0006-4971
SN 1528-0020
YR 2006
FD 2006-08-15
LK https://hdl.handle.net/20.500.14352/98451
UL https://hdl.handle.net/20.500.14352/98451
LA eng
NO Del-Rey M, Ruiz-Contreras J, Bosque A, Calleja S, Gomez-Rial J, Roldan E, Morales P, Serrano A, Anel A, Paz-Artal E, Allende LM. A homozygous Fas ligand gene mutation in a patient causes a new type of autoimmune lymphoproliferative syndrome. Blood. 2006 Aug 15;108(4):1306-12. doi: 10.1182/blood-2006-04-015776. Epub 2006 Apr 20. PMID: 16627752.
DS Docta Complutense
RD 20 dic 2025