Autoimmune lymphoproliferative syndrome (ALPS) in a child from consanguineous parents: A dominant or recessive disease?

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by autoimmu ne features and lymphoproliferations and is generally caused by defective F as-mediated apoptosis. This report describes a child with clinical features of ALPS without detectable Fas expression on freshly isolated blood leukoc ytes. Detection of FAS transcripts via real-time quantitative PCR made a se vere transcriptional defect unlikely. Sequencing of the FAS gene revealed a 20-nucleotide duplication in the last exon affecting the cytoplasmic signa ling domain. The patient was homozygous for this mutation, whereas the cons anguineous parents and the siblings were heterozygous. The patient reported here is a human homologue of the Fas-null mouse, inasmuch as she carries a n autosomal homozygous mutation in the FAS gene and she shows the severe an d accelerated ALPS phenotype. The heterozygous family members did not have the ALPS phenotype, indicating that the disease-causing FAS mutation in thi s family is autosomal recessive.