title: Autoimmune lymphoproliferative syndrome (ALPS) in a child from consanguineous parents: a dominant or recessive disease?
abstract: Autoimmune lymphoproliferative syndrome (ALPS) is characterized by autoimmune features and lymphoproliferations and is generally caused by defective Fas-mediated apoptosis. This report describes a child with clinical features of ALPS without detectable Fas expression on freshly isolated blood leukocytes. Detection of FAS transcripts via real-time quantitative PCR made a severe transcriptional defect unlikely. Sequencing of the FAS gene revealed a 20-nucleotide duplication in the last exon affecting the cytoplasmic signaling domain. The patient was homozygous for this mutation, whereas the consanguineous parents and the siblings were heterozygous. The patient reported here is a human homologue of the Fas-null mouse, inasmuch as she carries an autosomal homozygous mutation in the FAS gene and she shows the severe and accelerated ALPS phenotype. The heterozygous family members did not have the ALPS phenotype, indicating that the disease-causing FAS mutation in this family is autosomal recessive.
authors.affiliation: Department of Immunology, Erasmus University Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van der Burg
authors.forename: R
authors.initials: R
authors.lastname: de Groot
authors.forename: W M
authors.initials: WM
authors.lastname: Comans-Bitter
authors.forename: J C
authors.initials: JC
authors.lastname: den Hollander
authors.forename: H
authors.initials: H
authors.lastname: Hooijkaas
authors.forename: H J
authors.initials: HJ
authors.lastname: Neijens
authors.forename: R M
authors.initials: RM
authors.lastname: Berger
authors.forename: A P
authors.initials: AP
authors.lastname: Oranje
authors.forename: A W
authors.initials: AW
authors.lastname: Langerak
authors.forename: J J
authors.initials: JJ
authors.lastname: van Dongen
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D003241:Consanguinity; D017931:DNA Primers; D005091:Exons; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D019014:fas Receptor