Person:
Ruiz Contreras, Jesús

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First Name
Jesús
Last Name
Ruiz Contreras
URI
https://hdl.handle.net/20.500.14352/79407
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Salud Pública y Materno-Infantil
Area
Pediatría
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Author: Bosque, Alberto × End date: 2009 ×

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    A homozygous Fas ligand gene mutation in a patient causes a new type of autoimmune lymphoproliferative syndrome
    (Blood, 2006) Del-Rey, Manuel; Bosque, Alberto; Calleja, Sara; Gomez-Rial, Jose; Roldan, Ernesto; Morales, Pablo; Serrano, Antonio; Anel, Alberto; Ruiz Contreras, Jesús; Paz Artal, Estela Natividad; Allende Martínez, Luis Miguel
    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.