PubMed:9028321 JSONTXT

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":287,"end":292},"obj":"gene:355"},{"id":"T1","span":{"begin":444,"end":483},"obj":"disease:C1328840"},{"id":"T2","span":{"begin":287,"end":292},"obj":"gene:355"},{"id":"T3","span":{"begin":485,"end":489},"obj":"disease:C1328840"},{"id":"T4","span":{"begin":544,"end":547},"obj":"gene:355"},{"id":"T5","span":{"begin":444,"end":483},"obj":"disease:C1328840"},{"id":"T6","span":{"begin":544,"end":547},"obj":"gene:2194"},{"id":"T7","span":{"begin":444,"end":483},"obj":"disease:C1328840"},{"id":"T8","span":{"begin":544,"end":547},"obj":"gene:355"},{"id":"T9","span":{"begin":485,"end":489},"obj":"disease:C1328840"},{"id":"T10","span":{"begin":544,"end":547},"obj":"gene:2194"},{"id":"T11","span":{"begin":485,"end":489},"obj":"disease:C1328840"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"},{"id":"R5","pred":"associated_with","subj":"T8","obj":"T9"},{"id":"R6","pred":"associated_with","subj":"T10","obj":"T11"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"9028321-0#26#29#gene355","span":{"begin":26,"end":29},"obj":"gene355"},{"id":"9028321-0#48#87#diseaseC1328840","span":{"begin":48,"end":87},"obj":"diseaseC1328840"}],"relations":[{"id":"26#29#gene35548#87#diseaseC1328840","pred":"associated_with","subj":"9028321-0#26#29#gene355","obj":"9028321-0#48#87#diseaseC1328840"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"performance-test","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":1169,"end":1174},"obj":"http://purl.obolibrary.org/obo/UBERON_0001977"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":264,"end":277},"obj":"http://purl.obolibrary.org/obo/UBERON_0002405"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"sentences","denotations":[{"id":"TextSentencer_T1","span":{"begin":0,"end":128},"obj":"Sentence"},{"id":"TextSentencer_T2","span":{"begin":129,"end":278},"obj":"Sentence"},{"id":"TextSentencer_T3","span":{"begin":279,"end":553},"obj":"Sentence"},{"id":"TextSentencer_T4","span":{"begin":554,"end":730},"obj":"Sentence"},{"id":"TextSentencer_T5","span":{"begin":731,"end":875},"obj":"Sentence"},{"id":"TextSentencer_T6","span":{"begin":876,"end":1267},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":128},"obj":"Sentence"},{"id":"T2","span":{"begin":129,"end":278},"obj":"Sentence"},{"id":"T3","span":{"begin":279,"end":553},"obj":"Sentence"},{"id":"T4","span":{"begin":554,"end":730},"obj":"Sentence"},{"id":"T5","span":{"begin":731,"end":875},"obj":"Sentence"},{"id":"T6","span":{"begin":876,"end":1267},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"PubCasesHPO","denotations":[{"id":"AB1","span":{"begin":785,"end":797},"obj":"HP:0001744"},{"id":"AB2","span":{"begin":802,"end":817},"obj":"HP:0002716"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"UBERON-AE","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":264,"end":277},"obj":"http://purl.obolibrary.org/obo/UBERON_0002405"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":1169,"end":1174},"obj":"http://purl.obolibrary.org/obo/UBERON_0001977"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"PubCasesORDO","denotations":[{"id":"TI1","span":{"begin":48,"end":87},"obj":"ORDO:3261"},{"id":"AB1","span":{"begin":444,"end":483},"obj":"ORDO:3261"},{"id":"AB2","span":{"begin":485,"end":489},"obj":"ORDO:3261"},{"id":"AB3","span":{"begin":586,"end":590},"obj":"ORDO:3261"}],"namespaces":[{"prefix":"ORDO","uri":"http://www.orpha.net/ORDO/Orphanet_"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"NCBIDiseaseCorpus","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease:D056735"},{"id":"T2","span":{"begin":444,"end":483},"obj":"SpecificDisease:D056735"},{"id":"T3","span":{"begin":485,"end":489},"obj":"SpecificDisease:D056735"},{"id":"T4","span":{"begin":586,"end":590},"obj":"SpecificDisease:D056735"},{"id":"T5","span":{"begin":785,"end":797},"obj":"DiseaseClass:D013163"},{"id":"T6","span":{"begin":802,"end":817},"obj":"DiseaseClass:D008206"},{"id":"T7","span":{"begin":849,"end":874},"obj":"DiseaseClass:D001327"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"ncbi-valid-gpt-r-ng","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":374,"end":393},"obj":"DiseaseClass"},{"id":"T3","span":{"begin":444,"end":490},"obj":"CompositeMention"},{"id":"T4","span":{"begin":586,"end":590},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":785,"end":797},"obj":"SpecificDisease"},{"id":"T6","span":{"begin":802,"end":817},"obj":"SpecificDisease"},{"id":"T7","span":{"begin":842,"end":848},"obj":"Modifier"},{"id":"T8","span":{"begin":849,"end":874},"obj":"DiseaseClass"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"ncbi-valid-gpt-r-g","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T3","span":{"begin":485,"end":489},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":586,"end":590},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":785,"end":797},"obj":"SpecificDisease"},{"id":"T6","span":{"begin":802,"end":817},"obj":"SpecificDisease"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"ncbi-valid-gpt-nr-g","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T3","span":{"begin":485,"end":489},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":586,"end":590},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":785,"end":797},"obj":"SpecificDisease"},{"id":"T6","span":{"begin":802,"end":817},"obj":"SpecificDisease"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"ncbi-valid","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T3","span":{"begin":485,"end":489},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":586,"end":590},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":785,"end":797},"obj":"DiseaseClass"},{"id":"T6","span":{"begin":802,"end":817},"obj":"DiseaseClass"},{"id":"T7","span":{"begin":849,"end":874},"obj":"DiseaseClass"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"ncbi-valid-gemini-r-g","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":374,"end":393},"obj":"DiseaseClass"},{"id":"T3","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":485,"end":489},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":785,"end":797},"obj":"DiseaseClass"},{"id":"T6","span":{"begin":802,"end":817},"obj":"DiseaseClass"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"ncbi-valid-gpt-nr-ng","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":374,"end":393},"obj":"DiseaseClass"},{"id":"T3","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":485,"end":489},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":586,"end":590},"obj":"SpecificDisease"},{"id":"T6","span":{"begin":785,"end":817},"obj":"CompositeMention"},{"id":"T7","span":{"begin":842,"end":848},"obj":"Modifier"},{"id":"T8","span":{"begin":849,"end":874},"obj":"DiseaseClass"},{"id":"T9","span":{"begin":997,"end":1004},"obj":"Modifier"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"ncbi-valid-gemini-nr-g","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":374,"end":393},"obj":"DiseaseClass"},{"id":"T3","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":485,"end":489},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":785,"end":797},"obj":"SpecificDisease"},{"id":"T6","span":{"begin":802,"end":817},"obj":"SpecificDisease"},{"id":"T7","span":{"begin":842,"end":874},"obj":"DiseaseClass"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"ncbi-valid-gemini-nr-ng","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":374,"end":393},"obj":"SpecificDisease"},{"id":"T3","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":485,"end":489},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":842,"end":874},"obj":"DiseaseClass"},{"id":"T6","span":{"begin":976,"end":983},"obj":"DiseaseClass"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"ncbi-valid-deepseek-nr-ng","denotations":[{"id":"T1","span":{"begin":0,"end":18},"obj":"Modifier"},{"id":"T2","span":{"begin":26,"end":34},"obj":"CompositeMention"},{"id":"T3","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":155,"end":164},"obj":"DiseaseClass"},{"id":"T5","span":{"begin":283,"end":301},"obj":"CompositeMention"},{"id":"T6","span":{"begin":374,"end":393},"obj":"DiseaseClass"},{"id":"T7","span":{"begin":397,"end":413},"obj":"CompositeMention"},{"id":"T8","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T9","span":{"begin":485,"end":489},"obj":"SpecificDisease"},{"id":"T10","span":{"begin":544,"end":552},"obj":"CompositeMention"},{"id":"T11","span":{"begin":643,"end":661},"obj":"Modifier"},{"id":"T12","span":{"begin":720,"end":729},"obj":"DiseaseClass"},{"id":"T13","span":{"begin":785,"end":797},"obj":"DiseaseClass"},{"id":"T14","span":{"begin":802,"end":817},"obj":"DiseaseClass"},{"id":"T15","span":{"begin":849,"end":874},"obj":"DiseaseClass"},{"id":"T16","span":{"begin":931,"end":942},"obj":"CompositeMention"},{"id":"T17","span":{"begin":942,"end":946},"obj":"CompositeMention"},{"id":"T18","span":{"begin":946,"end":950},"obj":"CompositeMention"},{"id":"T19","span":{"begin":950,"end":968},"obj":"CompositeMention"},{"id":"T20","span":{"begin":976,"end":983},"obj":"CompositeMention"},{"id":"T21","span":{"begin":997,"end":1026},"obj":"DiseaseClass"},{"id":"T22","span":{"begin":1088,"end":1094},"obj":"CompositeMention"},{"id":"T23","span":{"begin":1120,"end":1123},"obj":"CompositeMention"},{"id":"T24","span":{"begin":1202,"end":1232},"obj":"CompositeMention"},{"id":"T25","span":{"begin":1234,"end":1240},"obj":"CompositeMention"},{"id":"T26","span":{"begin":1246,"end":1258},"obj":"CompositeMention"},{"id":"T27","span":{"begin":1260,"end":1265},"obj":"CompositeMention"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"ncbi-valid-deepseek-nr-g","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T3","span":{"begin":485,"end":489},"obj":"SpecificDisease"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"ncbi-valid-deepseek-r-g","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T3","span":{"begin":485,"end":489},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":586,"end":590},"obj":"SpecificDisease"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"ncbi-valid-deepseek-r-ng","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":374,"end":393},"obj":"DiseaseClass"},{"id":"T3","span":{"begin":485,"end":489},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":785,"end":797},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":802,"end":817},"obj":"SpecificDisease"},{"id":"T6","span":{"begin":849,"end":874},"obj":"DiseaseClass"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"ncbi-valid-gemini-r-ng","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":374,"end":393},"obj":"SpecificDisease"},{"id":"T3","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":485,"end":489},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":785,"end":797},"obj":"SpecificDisease"},{"id":"T6","span":{"begin":802,"end":817},"obj":"SpecificDisease"},{"id":"T7","span":{"begin":849,"end":874},"obj":"DiseaseClass"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"ncbi-valid-gemini-r-m","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":374,"end":393},"obj":"DiseaseClass"},{"id":"T3","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":485,"end":489},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":785,"end":797},"obj":"SpecificDisease"},{"id":"T6","span":{"begin":802,"end":817},"obj":"SpecificDisease"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"ncbi-valid-gpt-r-m","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T3","span":{"begin":485,"end":489},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":586,"end":590},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":785,"end":797},"obj":"DiseaseClass"},{"id":"T6","span":{"begin":802,"end":817},"obj":"DiseaseClass"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"ncbi-valid-deepseek-r-m","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T3","span":{"begin":485,"end":489},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":586,"end":590},"obj":"SpecificDisease"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"NCBI-Disease-Develop","denotations":[{"id":"T417","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T418","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T419","span":{"begin":485,"end":489},"obj":"SpecificDisease"},{"id":"T420","span":{"begin":586,"end":590},"obj":"SpecificDisease"},{"id":"T421","span":{"begin":785,"end":797},"obj":"DiseaseClass"},{"id":"T422","span":{"begin":802,"end":817},"obj":"DiseaseClass"},{"id":"T423","span":{"begin":849,"end":874},"obj":"DiseaseClass"}],"attributes":[{"id":"A417","pred":"database_id","subj":"T417","obj":"D056735"},{"id":"A418","pred":"database_id","subj":"T418","obj":"D056735"},{"id":"A419","pred":"database_id","subj":"T419","obj":"D056735"},{"id":"A420","pred":"database_id","subj":"T420","obj":"D056735"},{"id":"A421","pred":"database_id","subj":"T421","obj":"D013163"},{"id":"A422","pred":"database_id","subj":"T422","obj":"D008206"},{"id":"A423","pred":"database_id","subj":"T423","obj":"D001327"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"NCBI-Disease-Corpus-All","denotations":[{"id":"T417","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T418","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T419","span":{"begin":485,"end":489},"obj":"SpecificDisease"},{"id":"T420","span":{"begin":586,"end":590},"obj":"SpecificDisease"},{"id":"T421","span":{"begin":785,"end":797},"obj":"DiseaseClass"},{"id":"T422","span":{"begin":802,"end":817},"obj":"DiseaseClass"},{"id":"T423","span":{"begin":849,"end":874},"obj":"DiseaseClass"}],"attributes":[{"id":"A417","pred":"database_id","subj":"T417","obj":"D056735"},{"id":"A418","pred":"database_id","subj":"T418","obj":"D056735"},{"id":"A419","pred":"database_id","subj":"T419","obj":"D056735"},{"id":"A420","pred":"database_id","subj":"T420","obj":"D056735"},{"id":"A421","pred":"database_id","subj":"T421","obj":"D013163"},{"id":"A422","pred":"database_id","subj":"T422","obj":"D008206"},{"id":"A423","pred":"database_id","subj":"T423","obj":"D001327"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"NCBI-Disease-Corpus-2stage-All","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":374,"end":393},"obj":"SpecificDisease"},{"id":"T3","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":485,"end":489},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":586,"end":590},"obj":"SpecificDisease"},{"id":"T6","span":{"begin":802,"end":817},"obj":"SpecificDisease"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"NCBI-Disease-Corpus-rezarta-All","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":374,"end":393},"obj":"DiseaseClass"},{"id":"T3","span":{"begin":444,"end":483},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":586,"end":590},"obj":"SpecificDisease"},{"id":"T5","span":{"begin":785,"end":797},"obj":"SpecificDisease"},{"id":"T6","span":{"begin":802,"end":817},"obj":"SpecificDisease"},{"id":"T7","span":{"begin":849,"end":874},"obj":"DiseaseClass"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"NCBI-Disease-Corpus-4oGuideline-All","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":444,"end":490},"obj":"SpecificDisease"},{"id":"T3","span":{"begin":586,"end":590},"obj":"SpecificDisease"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}

{"project":"NCBI-Disease-Corpus-Simple-All","denotations":[{"id":"T1","span":{"begin":48,"end":87},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":155,"end":164},"obj":"DiseaseClass"},{"id":"T3","span":{"begin":344,"end":353},"obj":"DiseaseClass"},{"id":"T4","span":{"begin":374,"end":393},"obj":"DiseaseClass"},{"id":"T5","span":{"begin":444,"end":490},"obj":"SpecificDisease"},{"id":"T6","span":{"begin":586,"end":590},"obj":"SpecificDisease"},{"id":"T7","span":{"begin":720,"end":729},"obj":"DiseaseClass"},{"id":"T8","span":{"begin":785,"end":797},"obj":"Modifier"},{"id":"T9","span":{"begin":802,"end":817},"obj":"Modifier"},{"id":"T10","span":{"begin":849,"end":874},"obj":"CompositeMention"}],"text":"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.\nProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4-CD8- (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (slL-2R) and soluble CD30 (sCD30)."}