CNV results and clinical phenotypes of probands with autoimmune lymphoproliferative syndrome
| . | Subject 1 (140.1) . | Subject 2 (384.1) . | Subject 3 (396.1) . |
|---|---|---|---|
| CNV results | |||
| Size of copy number loss, Mb | 0.828 | 1.004 | 0.044 |
| Exons affected | All | All | 7-9 |
| Genomic location | 10q23.31 | 10q23.31 | 10q23.31 |
| Probes, no. | 15 | 63 | 15 |
| Parental studies | De novo copy number loss | Maternally inherited, mother with mild neutropenia and no other manifestations | Paternally inherited, father unaffected |
| Clinical phenotypes | |||
| Age, y | 34 | 11 | 14 |
| Race | Caucasian | Asian | Caucasian |
| Age of onset, y | 5 | 2 | 5 |
| Presenting symptoms | Arthralgias, autoimmune fevers, diarrhea, and autoimmune hemolytic anemia, adenopathy, splenomegaly, pancytopenia, and follicular hyperplasia | Severe pancytopenia, hepatosplenomegaly, and lymphadenopathy | Fatigue, abdominal pain, cytopenias, lymphadenopathy, and splenomegaly |
| Treatment | Prednisone pulses No sirolimus No mycophenolate | Mycophenolate | Mycophenolate with poor response, sirolimus with good effect |
| Required criteria | |||
| Splenomegaly | + | + | + |
| Lymphadenopathy | + | + | + |
| Elevated CD3+ αβ+ CD4−CD8− DNT cells (>1.5% of total lymphocytes or >2.5% of CD3+ lymphocytes) with normal or elevated lymphocyte counts | + | + | + |
| Accessory criteria | |||
| Primary criteria | |||
| Defective FAS-induced apoptosis | + (22.2%; absolute of 325) | NR (9.25%; no absolute provided) | + |
| Somatic or germline pathogenic mutation in FAS, FASL, FADD, or CASP10 | – | – | – |
| Secondary criteria | |||
| Hemolytic anemia | + | + | + |
| Thrombocytopenia | + | + | + |
| Neutropenia | + | + | + |
| Serum elevated B12 levels (>1500 pg/mL) | + | + | + |
| Elevated plasma sFASL levels (>200 pg/mL) | – | + (2193 pg/mL) | – |
| Elevated plasma interleukin-10 levels (>20 pg/mL) | NR | + (27 pg/mL) | + |
| Typical immunohistopathology findings (paracortical T-cell hyperplasia) | – | + | – |
| Elevated immunoglobulin G levels (polyclonal hypergammaglobinemia) | + | + | + |
| Family history of a nonmalignant or lymphoma-associated noninfectious lymphoproliferation with or without autoimmunity | – | – | – |
| . | Subject 1 (140.1) . | Subject 2 (384.1) . | Subject 3 (396.1) . |
|---|---|---|---|
| CNV results | |||
| Size of copy number loss, Mb | 0.828 | 1.004 | 0.044 |
| Exons affected | All | All | 7-9 |
| Genomic location | 10q23.31 | 10q23.31 | 10q23.31 |
| Probes, no. | 15 | 63 | 15 |
| Parental studies | De novo copy number loss | Maternally inherited, mother with mild neutropenia and no other manifestations | Paternally inherited, father unaffected |
| Clinical phenotypes | |||
| Age, y | 34 | 11 | 14 |
| Race | Caucasian | Asian | Caucasian |
| Age of onset, y | 5 | 2 | 5 |
| Presenting symptoms | Arthralgias, autoimmune fevers, diarrhea, and autoimmune hemolytic anemia, adenopathy, splenomegaly, pancytopenia, and follicular hyperplasia | Severe pancytopenia, hepatosplenomegaly, and lymphadenopathy | Fatigue, abdominal pain, cytopenias, lymphadenopathy, and splenomegaly |
| Treatment | Prednisone pulses No sirolimus No mycophenolate | Mycophenolate | Mycophenolate with poor response, sirolimus with good effect |
| Required criteria | |||
| Splenomegaly | + | + | + |
| Lymphadenopathy | + | + | + |
| Elevated CD3+ αβ+ CD4−CD8− DNT cells (>1.5% of total lymphocytes or >2.5% of CD3+ lymphocytes) with normal or elevated lymphocyte counts | + | + | + |
| Accessory criteria | |||
| Primary criteria | |||
| Defective FAS-induced apoptosis | + (22.2%; absolute of 325) | NR (9.25%; no absolute provided) | + |
| Somatic or germline pathogenic mutation in FAS, FASL, FADD, or CASP10 | – | – | – |
| Secondary criteria | |||
| Hemolytic anemia | + | + | + |
| Thrombocytopenia | + | + | + |
| Neutropenia | + | + | + |
| Serum elevated B12 levels (>1500 pg/mL) | + | + | + |
| Elevated plasma sFASL levels (>200 pg/mL) | – | + (2193 pg/mL) | – |
| Elevated plasma interleukin-10 levels (>20 pg/mL) | NR | + (27 pg/mL) | + |
| Typical immunohistopathology findings (paracortical T-cell hyperplasia) | – | + | – |
| Elevated immunoglobulin G levels (polyclonal hypergammaglobinemia) | + | + | + |
| Family history of a nonmalignant or lymphoma-associated noninfectious lymphoproliferation with or without autoimmunity | – | – | – |
NR, not reported.