title: Polymorphisms in FAS and CASP8 genes may contribute to the development of ALPS phenotype: a study in 25 patients with probable ALPS.
abstract: Defects in genes that have role in apoptotic pathways result in development of Autoimmune Lymphoproliferative Syndrome (ALPS) and ALPS related disorders. Germline and somatic FAS mutations, FASL and CASP10 mutations constitute other genetic defects in ALPS. Patients who fulfill ALPS diagnostic criteria and do not have any identified known disease causing mutations are classified as ALPS-unknown or ALPS phenotype and comprise about one third of all patients. CASP8, NRAS and KRAS gene mutations were reported for ALPS related diseases. We performed DNA sequence analysis in 25 unrelated patients with probable ALPS for FAS, FASL and CASP8 gene defects. Pathogenic mutations could not be found in the FAS, FASL and CASP8 genes. However, we found that the frequencies of SNPs rs2234978 and rs1045487 of FAS and CASP8 genes were significantly higher in the patients. Our results suggest that CASP8 and FAS gene polymorphisms in particular, may contribute to the susceptibility to development of ALPS phenotype.
authors.affiliation: Division of Immunology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara. cagmantan@gmail.com.
authors.forename: Çağman
authors.initials: Ç
authors.lastname: Tan
authors.forename: Rıza Köksal
authors.initials: RK
authors.lastname: Özgül
authors.forename: Deniz
authors.initials: D
authors.lastname: Çağdaş Ayvaz
authors.forename: İlhan
authors.initials: İ
authors.lastname: Tezcan
authors.forename: Özden
authors.initials: Ö
authors.lastname: Sanal
mesh_terms: D017209:Apoptosis; D016022:Case-Control Studies; D053181:Caspase 8 / Q000235:genetics*; D053222:Fas Ligand Protein / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D013577:Syndrome; D019014:fas Receptor / Q000235:genetics*
chemical_list: D053222:Fas Ligand Protein; D019014:fas Receptor; C505530:CASP8 protein, human; D053181:Caspase 8