title: Germline FAS gene mutation in a case of ALPS and NLP Hodgkin lymphoma.
abstract: FAS germline mutations have been associated with the development of autoimmune lymphoproliferative syndrome (ALPS). Occurrence of Hodgkin lymphoma (HL) has been reported in 2 families with ALPS. In both families an uncle of the index patient developed HL. A 15-year-old boy with autoimmune thrombopenia, lymphadenopathy, and splenomegaly for 6 years was studied. In an axillary lymph node biopsy nodular lymphocyte predominant (NLP) HL was diagnosed; in the areas between the nodules a proliferation of double-negative blastic T cells were present, suggestive of ALPS. Analysis for the presence of a FAS gene mutation using the denaturing gradient gel electrophoresis technique indicated a mutation in exon 9. Direct sequence analysis revealed a mutation causing a substitution of arginine with glutamine at codon 234. Because ALPS and NLP HL are both highly infrequent conditions, the occurrence in at least 3 families suggests a causative relationship between germline FAS gene mutations and NLP HL.
authors.affiliation: Department of Pathology and Laboratory Medicine, University Hospital Groningen, The Netherlands.
authors.forename: Anke
authors.initials: A
authors.lastname: van den Berg
authors.forename: Ewerton
authors.initials: E
authors.lastname: Maggio
authors.forename: Arjan
authors.initials: A
authors.lastname: Diepstra
authors.forename: Debora
authors.initials: D
authors.lastname: de Jong
authors.forename: Johan
authors.initials: J
authors.lastname: van Krieken
authors.forename: Sibrand
authors.initials: S
authors.lastname: Poppema
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D001327:Autoimmune Diseases / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D018095:Germ-Line Mutation; D006689:Hodgkin Disease / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D008297:Male; D013601:T-Lymphocytes / Q000473:pathology; D019014:fas Receptor / Q000235:genetics*
chemical_list: D019014:fas Receptor