title: A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation.
abstract: Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disorder characterized by early-onset, chronic, nonmalignant lymphoproliferation, autoimmune manifestations, and susceptibility to lymphoma. The majority of ALPS patients carry heterozygous germline (ALPS-FAS) or somatic mutations (ALPS-sFAS) of the TNFRSF6 gene coding for FAS. Although the clinical features of ALPS have been described previously, long-term follow-up data on morbidity and mortality are scarce. We performed a retrospective analysis of clinical and genetic features of 90 ALPS-FAS and ALPS-sFAS patients monitored over a median period of 20.5 years. Heterozygous germline mutations of TNFRSF6 were identified in 83% of probands. Somatic TNFRSF6 mutations were found in 17% of index cases (all located within the intracellular domain of FAS). Sixty percent of the ALPS-FAS patients with mutations in the extracellular domain had a somatic mutation affecting the second allele of TNFRSF6; age at onset was later in these patients. No other genotype-phenotype correlations could be found. Long-term analysis confirmed a trend toward spontaneous remission of lymphoproliferation in adulthood but mixed outcomes for autoimmune manifestations. We observed significant and potentially life-threatening disease and treatment-related morbidity, including a high risk of sepsis after splenectomy that calls for careful long-term monitoring of ALPS patients. We also noted a significantly greater occurrence of disease-related symptoms in male than in female patients.
authors: Inserm U768, Hôpital Necker-Enfants Malades, Paris, France. benedicte.neven@nck.aphp.fr
authors: Bénédicte
authors: B
authors: Neven
authors: Aude
authors: A
authors: Magerus-Chatinet
authors: Benoit
authors: B
authors: Florkin
authors: Delphine
authors: D
authors: Gobert
authors: Olivier
authors: O
authors: Lambotte
authors: Lien
authors: L
authors: De Somer
authors: Nina
authors: N
authors: Lanzarotti
authors: Marie-Claude
authors: MC
authors: Stolzenberg
authors: Brigitte
authors: B
authors: Bader-Meunier
authors: Nathalie
authors: N
authors: Aladjidi
authors: Christophe
authors: C
authors: Chantrain
authors: Yves
authors: Y
authors: Bertrand
authors: Eric
authors: E
authors: Jeziorski
authors: Guy
authors: G
authors: Leverger
authors: Gérard
authors: G
authors: Michel
authors: Felipe
authors: F
authors: Suarez
authors: Eric
authors: E
authors: Oksenhendler
authors: Olivier
authors: O
authors: Hermine
authors: Stéphane
authors: S
authors: Blanche
authors: Capucine
authors: C
authors: Picard
authors: Alain
authors: A
authors: Fischer
authors: Frédéric
authors: F
authors: Rieux-Laucat
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D056735:Autoimmune Lymphoproliferative Syndrome / Q000097:blood / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003625:Data Collection; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D055815:Young Adult; D019014:fas Receptor / Q000235:genetics*
chemical_list: C491901:FAS protein, human; D019014:fas Receptor