XLP1
MCID: LYM113
MIFTS: 61

Lymphoproliferative Syndrome, X-Linked, 1 (XLP1)

Categories: Blood diseases, Genetic diseases, Immune diseases, Rare diseases

Aliases & Classifications for Lymphoproliferative Syndrome, X-Linked, 1

MalaCards integrated aliases for Lymphoproliferative Syndrome, X-Linked, 1:

Name: Lymphoproliferative Syndrome, X-Linked, 1 56 52 73
X-Linked Lymphoproliferative Syndrome 74 52 25 36 54 6
Purtilo Syndrome 56 74 52 25 58 73
Duncan Disease 56 24 52 25 58 73
Xlp1 56 12 52 58 73
Xlp 56 24 52 25 58
X-Linked Lymphoproliferative Disease 52 25 58 73
X-Linked Lymphoproliferative Syndrome 1 12 52 15
Lymphoproliferative Disease, X-Linked 56 24 52
Xlpd 56 52 73
X-Linked Lymphoproliferative Disease Due to Sh2d1a Deficiency 52 58
Ebv Infection, Severe, Susceptibility to 56 52
Lymphoproliferative Syndrome 1, X-Linked 29 6
Immunodeficiency 5 56 73
Ebvs 56 52
Imd5 56 73
Lyp 56 74
Epstein-Barr Virus-Induced Lymphoproliferative Disease in Males 25
X-Linked Progressive Combined Variable Immunodeficiency 5 52
Immunodeficiency, X-Linked Progressive Combined Variable 56
X-Linked Progressive Combined Variable Immunodeficiency 73
Sh2d1a-Related Lymphoproliferative Disease, X-Linked 52
Infectious Mononucleosis, Severe, Susceptibility to 56
Severe Susceptibility to Infectious Mononucleosis 25
Lymphoproliferative Syndrome, X-Linked, Type 1 39
Epstein-Barr Virus Infection, Familial Fatal 56
Epstein Barr Virus Infection, Familial Fatal 52
X-Linked Lymphoproliferative Syndrome Type 1 58
Lymphoproliferative Disease, X-Linked; Xlpd 56
Sh2d1a/slam-Associated Protein Deficiency 58
Lymphoproliferative Syndrome X-Linked 1 52
Severe Susceptibility to Ebv Infection 25
Lymphoproliferative Syndrome, X-Linked 13
Familial Fatal Epstein-Barr Infection 25
X-Linked Lymphoproliferative Disorder 71
Infectious Mononucleosis, Severe 56
Ebv Infection, Severe ; Ebvs 56
Immunodeficiency 5; Imd5 56
Sap Deficiency 58
Sap 17

Characteristics:

Orphanet epidemiological data:

58
x-linked lymphoproliferative disease
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Europe); Age of onset: Childhood;

OMIM:

56
Inheritance:
x-linked recessive

Miscellaneous:
reduced life expectancy, death by 10 years of age in 70% of patients


HPO:

31
lymphoproliferative syndrome, x-linked, 1:
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare immunological diseases


External Ids:

Disease Ontology 12 DOID:0060705
OMIM 56 308240
OMIM Phenotypic Series 56 PS300755 PS308240
KEGG 36 H01969
MeSH 43 D008232
ICD10 32 D82.3
MESH via Orphanet 44 D008232
ICD10 via Orphanet 33 D82.3
UMLS via Orphanet 72 C0549463
UMLS 71 C0549463

Summaries for Lymphoproliferative Syndrome, X-Linked, 1

NIH Rare Diseases : 52 X-linked lymphoproliferative syndrome (XLP) is an immune system disorder that occurs almost exclusively in males. People with XLP have an increased risk of infection because their body cannot properly regulate the number of immune system cells (lymphocytes ) and blood cells. The symptoms associated with XLP vary from person to person, and even among family members. In most cases, symptoms begin anywhere from 6 months of age to 10 years of age. XLP generally has two subtypes, which are caused by mutations in different genes : XLP1 is mainly characterized by an inappropriate immune response to Epstein-Barr virus (EBV) infection , leading to hemophagocytic lymphohistiocytosis (HLH) or severe mononucleosis ; dysgammaglobulinemia; and lymphoproliferative disease (malignant lymphoma). XLP2 is usually characterized by HLH (often associated with EBV), dysgammaglobulinemia, and inflammatory bowel disease (colitis). People with XLP2 have not been known to develop lymphoma. Signs and symptoms of HLH include fever, enlarged lymph nodes and spleen, skin rashes, and problems with the lungs, digestive system, liver, and nervous system. The heart, kidneys, or other organs may also be affected. Mononucleosis may cause fatigue; fever; an inflamed and sore throat; enlarged lymph nodes, liver, and spleen; and symptoms of anemia . Dysgammaglobulinemia causes an increased risk of recurrent infections. XLP1 is caused by mutations in the SH2D1A gene, and XLP2 is caused by mutations in the XIAP gene. Inheritance is X-linked recessive . However, in rare cases, females with a mutation on one copy of the responsible gene develop symptoms of XLP. A diagnosis of either type of XLP can be confirmed with genetic testing . Of note, there have been males with mutations known to cause XLP that have not developed symptoms. The only cure for XLP is allogeneic hematopoietic cell transplantation , which should be considered as early as possible. Treatment of XLP-related HLH may include immunosuppressive agents (such as steroids and etoposide or anti-thymocyte globulin ), and rituximab when HLH is associated with EBV infection. Hypogammaglobulinemia is treated with IVIG replacement therapy , and lymphoma is treated with standard chemotherapy . Inflammatory bowel disease is treated with immunosuppression. Without treatment, many people with XLP do not survive beyond childhood, usually due to HLH. The average age of death for males has been reported as 11 years (with a range of 2-69 years) for XLP1, and 16 years (with a range of 1-52 years) for XLP2.

MalaCards based summary : Lymphoproliferative Syndrome, X-Linked, 1, also known as x-linked lymphoproliferative syndrome, is related to immunodeficiency, x-linked, with magnesium defect, epstein-barr virus infection, and neoplasia and hemophagocytic lymphohistiocytosis, familial, 1. An important gene associated with Lymphoproliferative Syndrome, X-Linked, 1 is SH2D1A (SH2 Domain Containing 1A), and among its related pathways/superpathways are Natural killer cell mediated cytotoxicity and Apoptosis. The drugs Cytarabine and Cyclophosphamide have been mentioned in the context of this disorder. Affiliated tissues include t cells, b cells and kidney, and related phenotypes are cellular immunodeficiency and splenomegaly

Disease Ontology : 12 A lymphoproliferative syndrome characterized by severe immune dysregulation after viral infect that may manifest as severe or fatal mononucleosis, acquired hypogammaglobulinema, hemophagocytic lymphohistiocytosis, and/or malignant lymphoma and that has material basis in X-linked mutation in the SH2D1A gene on chromosome Xq25.

Genetics Home Reference : 25 X-linked lymphoproliferative disease (XLP) is a disorder of the immune system and blood-forming cells that is found almost exclusively in males. More than half of individuals with this disorder experience an exaggerated immune response to the Epstein-Barr virus (EBV). EBV is a very common virus that eventually infects most humans. In some people it causes infectious mononucleosis (commonly known as "mono"). Normally, after initial infection, EBV remains in certain immune system cells (lymphocytes) called B cells. However, the virus is generally inactive (latent) because it is controlled by other lymphocytes called T cells that specifically target EBV-infected B cells. People with XLP may respond to EBV infection by producing abnormally large numbers of T cells, B cells, and other lymphocytes called macrophages. This proliferation of immune cells often causes a life-threatening reaction called hemophagocytic lymphohistiocytosis. Hemophagocytic lymphohistiocytosis causes fever, destroys blood-producing cells in the bone marrow, and damages the liver. The spleen, heart, kidneys, and other organs and tissues may also be affected. In some individuals with XLP, hemophagocytic lymphohistiocytosis or related symptoms may occur without EBV infection. About one-third of people with XLP experience dysgammaglobulinemia, which means they have abnormal levels of some types of antibodies. Antibodies (also known as immunoglobulins) are proteins that attach to specific foreign particles and germs, marking them for destruction. Individuals with dysgammaglobulinemia are prone to recurrent infections. Cancers of immune system cells (lymphomas) occur in about one-third of people with XLP. Without treatment, most people with XLP survive only into childhood. Death usually results from hemophagocytic lymphohistiocytosis. XLP can be divided into two types based on its genetic cause and pattern of signs and symptoms: XLP1 (also known as classic XLP) and XLP2. People with XLP2 have not been known to develop lymphoma, are more likely to develop hemophagocytic lymphohistiocytosis without EBV infection, usually have an enlarged spleen (splenomegaly), and may also have inflammation of the large intestine (colitis). Some researchers believe that these individuals should actually be considered to have a similar but separate disorder rather than a type of XLP.

OMIM : 56 X-linked lymphoproliferative syndrome, or Duncan disease, is a primary immunodeficiency characterized by severe immune dysregulation often after viral infection, typically with Epstein-Barr virus (EBV). It is a complex phenotype manifest as severe or fatal mononucleosis, acquired hypogammaglobulinema, hemophagocytic lymphohistiocytosis (HLH), and/or malignant lymphoma. Other features may include aplastic anemia, red cell aplasia, and lymphomatoid granulomatosis (Purtilo et al., 1977; Purtilo, 1981; Purtilo and Grierson, 1991; Coffey et al., 1998; Booth et al., 2011). (308240)

KEGG : 36 The X-linked lymphoproliferative syndrome (XLP) is a rare, inherited immunodeficiency that is characterized by lymphohystiocytosis, hypogammaglobulinaemia and lymphomas, and that usually develops in response to infection with Epstein-Barr virus (EBV). Mutations in the SH2D1A/SAP gene, a signalling adaptor molecule, underlie 60% of cases of familial XLP. Recently, mutations in the XIAP gene have been identified in patients with XLP.

UniProtKB/Swiss-Prot : 73 Lymphoproliferative syndrome, X-linked, 1: A rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.

Wikipedia : 74 Lymphomatoid papulosis (LyP) is a rare skin disorder. The overall prevalence rate of lymphomatoid... more...

GeneReviews: NBK1406

Related Diseases for Lymphoproliferative Syndrome, X-Linked, 1

Diseases in the Lymphoproliferative Syndrome, X-Linked, 1 family:

Lymphoproliferative Syndrome, X-Linked, 2

Diseases related to Lymphoproliferative Syndrome, X-Linked, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 829)
# Related Disease Score Top Affiliating Genes
1 immunodeficiency, x-linked, with magnesium defect, epstein-barr virus infection, and neoplasia 32.5 SLAMF6 SH2D1A MAGT1 ITK
2 hemophagocytic lymphohistiocytosis, familial, 1 31.1 UNC13D STXBP2 STX11 SH2D1A RAB27A PRF1
3 lymphoproliferative syndrome 2 31.1 XIAP STXBP2 SLAMF1 SH2D1A MAGT1 ITK
4 pfeiffer syndrome 30.8 SLAMF6 SLAMF1 SH2D1A PTPN11
5 lymphoproliferative syndrome 1 30.6 XIAP UNC13D STXBP2 STX11 SH2D1A PRF1
6 primary hemophagocytic lymphohistiocytosis 29.7 UNC13D STX11 RAB27A PRF1
7 hemophagocytic lymphohistiocytosis, familial, 3 29.4 UNC13D STX11 RAB27A
8 coronin-1a deficiency 29.3 SH2D1A MAGT1 ITK
9 autoimmune lymphoproliferative syndrome 29.3 UNC13D SH2D1A PRF1 MAGT1
10 macrophage activation syndrome 29.1 UNC13D RAB27A PRF1
11 lymphoproliferative syndrome, x-linked, 2 28.8 XIAP UNC13D STXBP2 STX11 SLAMF1 SH2D1A
12 myeloma, multiple 28.8 XIAP SLAMF7 SLAMF1 PTPN11 PRF1
13 lymphoproliferative syndrome 28.7 XIAP UNC13D SLAMF6 SLAMF1 SH2D1A PTPN11
14 pancytopenia 28.4 XIAP UNC13D STXBP2 STX11 SH2D1A RAB27A
15 hemophagocytic lymphohistiocytosis 27.6 XIAP UNC13D STXBP2 STX11 SH2D1A RAB27A
16 dysgammaglobulinemia 27.2 XIAP UNC13D STXBP2 STX11 SLAMF7 SLAMF6
17 lymphomatoid papulosis 12.5
18 combined saposin deficiency 12.1
19 chronic active epstein-barr virus infection 11.9
20 post-transplant lymphoproliferative disease 11.9
21 metachromatic leukodystrophy due to saposin b deficiency 11.7
22 immunodeficiency 64 11.7
23 systemic epstein-barr virus-positive t-cell lymphoma of childhood 11.7
24 nasopharyngeal carcinoma 11.6
25 systemic epstein-barr virus-positive t-cell lymphoproliferative disease of childhood 11.6
26 primary central nervous system lymphoma 11.6
27 epstein-barr virus-associated gastric carcinoma 11.5
28 epstein-barr virus-associated malignant lymphoproliferative disorder 11.5
29 epstein-barr virus-positive diffuse large b-cell lymphoma of the elderly 11.5
30 epstein-barr virus-associated carcinoma 11.5
31 epstein-barr virus-related tumor 11.5
32 oral hairy leukoplakia 11.4
33 immunodeficiency 58 11.3
34 immunodeficiency, common variable, 5 11.3
35 congenital epstein-barr virus infection 11.3
36 protoporphyria, erythropoietic, x-linked 11.3
37 immunodeficiency 20 11.2
38 immunodeficiency 24 11.2
39 lymphoproliferative syndrome 3 11.2
40 immunodeficiency 32b 11.1
41 epstein-barr virus-associated mesenchymal tumor 11.1
42 aminoacylase 1 deficiency 11.1
43 infections, recurrent, with encephalopathy, hepatic dysfunction, and cardiovascular malformations 11.1
44 immunodeficiency 14 11.1
45 b-cell expansion with nfkb and t-cell anergy 11.1
46 acute retinal necrosis syndrome 11.1
47 intraocular lymphoma 11.1
48 agammaglobulinemia 10.6
49 severe combined immunodeficiency 10.6
50 lymphopenia 10.5

Graphical network of the top 20 diseases related to Lymphoproliferative Syndrome, X-Linked, 1:



Diseases related to Lymphoproliferative Syndrome, X-Linked, 1

Symptoms & Phenotypes for Lymphoproliferative Syndrome, X-Linked, 1

Human phenotypes related to Lymphoproliferative Syndrome, X-Linked, 1:

58 31 (show all 19)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 cellular immunodeficiency 58 31 hallmark (90%) Very frequent (99-80%) HP:0005374
2 splenomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0001744
3 hepatomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0002240
4 decreased antibody level in blood 58 31 frequent (33%) Frequent (79-30%) HP:0004313
5 lymphoma 58 31 frequent (33%) Frequent (79-30%) HP:0002665
6 lymphadenopathy 58 31 frequent (33%) Frequent (79-30%) HP:0002716
7 anemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001903
8 encephalitis 31 HP:0002383
9 immunodeficiency 31 HP:0002721
10 pancytopenia 31 HP:0001876
11 thrombocytopenia 31 HP:0001873
12 recurrent pharyngitis 31 HP:0100776
13 meningitis 31 HP:0001287
14 decreased circulating igg level 31 HP:0004315
15 lymphocytosis 31 HP:0100827
16 fulminant hepatitis 31 HP:0004787
17 hepatic encephalopathy 31 HP:0002480
18 increased circulating igm level 31 HP:0003496
19 reduced natural killer cell activity 31 HP:0012178

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
encephalitis
meningitis
hepatic encephalopathy

Abdomen Liver:
hepatomegaly
fulminant hepatitis
liver failure

Neoplasia:
lymphoma
hemophagocytic lymphohistiocytosis

Respiratory Nasopharynx:
pharyngitis

Respiratory Lung:
lymphoid granulomatosis

Abdomen Spleen:
splenomegaly

Hematology:
anemia
pancytopenia
thrombocytopenia
atypical lymphocytosis

Immunology:
lymphadenopathy
reduced natural killer cell activity
normal number of b cells
normal number of t cells
combined variable immunodeficiency involving b and t cells
more
Laboratory Abnormalities:
reduced igg levels
increased igm levels

Clinical features from OMIM:

308240

GenomeRNAi Phenotypes related to Lymphoproliferative Syndrome, X-Linked, 1 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-4 10.05 ITK
2 Decreased viability GR00301-A 10.05 ITK
3 Decreased viability GR00342-S-1 10.05 ITK
4 Decreased viability GR00342-S-2 10.05 ITK
5 Decreased viability GR00342-S-3 10.05 ITK
6 Decreased viability GR00402-S-2 10.05 AP3B1 CD244 CD48 CD84 ITK LY9
7 no effect GR00402-S-1 9.62 AP3B1 CD244 CD48 CD84 ITK LY9

MGI Mouse Phenotypes related to Lymphoproliferative Syndrome, X-Linked, 1:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 10.13 AP3B1 CD244 CD48 CD84 ITK LY9
2 homeostasis/metabolism MP:0005376 9.73 AP3B1 CD84 LYST PRF1 PTPN11 RAB27A
3 immune system MP:0005387 9.62 AP3B1 CD244 CD48 CD84 ITK LY9

Drugs & Therapeutics for Lymphoproliferative Syndrome, X-Linked, 1

Drugs for Lymphoproliferative Syndrome, X-Linked, 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 51)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Cytarabine Approved, Experimental, Investigational Phase 2 147-94-4, 65-46-3 6253
2
Cyclophosphamide Approved, Investigational Phase 2 50-18-0, 6055-19-2 2907
3
Busulfan Approved, Investigational Phase 2 55-98-1 2478
4
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
5
alemtuzumab Approved, Investigational Phase 2 216503-57-0
6 Anti-Infective Agents Phase 2
7 Antimetabolites Phase 2
8 Antineoplastic Agents, Immunological Phase 2
9 Antiviral Agents Phase 2
10 Immunologic Factors Phase 2
11 Alkylating Agents Phase 2
12 Immunosuppressive Agents Phase 2
13 Antirheumatic Agents Phase 2
14 Tin Fluorides Phase 2
15
Lenograstim Approved, Investigational 135968-09-1
16
Methotrexate Approved 1959-05-2, 59-05-2 126941
17
leucovorin Approved 58-05-9 6006 143
18
Miconazole Approved, Investigational, Vet_approved 22916-47-8 4189
19
Etoposide Approved 33419-42-0 36462
20
Methylprednisolone Approved, Vet_approved 83-43-2 6741
21
Methylprednisolone hemisuccinate Approved 2921-57-5
22
Prednisolone Approved, Vet_approved 50-24-8 5755
23 Prednisolone acetate Approved, Vet_approved 52-21-1
24
Prednisone Approved, Vet_approved 53-03-2 5865
25
Prednisolone phosphate Approved, Vet_approved 302-25-0
26
Folic acid Approved, Nutraceutical, Vet_approved 59-30-3 6037
27
Prednisolone hemisuccinate Experimental 2920-86-7
28 Cola
29 Folic Acid Antagonists
30 Topoisomerase Inhibitors
31 Antilymphocyte Serum
32 Dermatologic Agents
33 Folate
34 Cyclosporins
35 Vitamin B9
36 Antifungal Agents
37 Calcineurin Inhibitors
38 Etoposide phosphate
39 Vitamin B Complex
40 Antiemetics
41 Methylprednisolone Acetate
42 Neuroprotective Agents
43 Hormone Antagonists
44 Complement System Proteins
45 Gastrointestinal Agents
46 Protective Agents
47 Autonomic Agents
48 Antineoplastic Agents, Hormonal
49 glucocorticoids
50 Anti-Inflammatory Agents

Interventional clinical trials:

(show all 13)
# Name Status NCT ID Phase Drugs
1 Phase I/II Trial Of Hematopoietic Stem Cell Transplant (HSCT) For Children With A Genetic Disease Of Blood Cells Without An HLA-Matched Sibling Donor Completed NCT00730314 Phase 1, Phase 2
2 CD-34 Selection for Ex-vivo T-Cell Depletion of Mobilized Peripheral Blood Stem Cells for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts Receiving Intensive Conditioning Recruiting NCT00368355 Phase 2 Ara-C;Cyclophosphamide
3 Protocol for Related Donor Hematopoietic Stem Cell Transplantation (HSCT) for Treatment of Symptomatic Genetic Lymphohematological Diseases Terminated NCT02512679 Phase 2 Cyclophosphamide Dose Level 1;Cyclophosphamide Dose Level 2;Cyclophosphamide Dose Level 3;Cyclophosphamide Dose Level 4
4 Administration of Haploidentical Donor T Cells Transduced With the Inducible Caspase-9 Suicide Gene Active, not recruiting NCT01494103 Phase 1 AP1903
5 CASPALLO: A Phase I Study Evaluating the Use of Allodepleted T Cells Transduced With Inducible Caspase 9 Suicide Gene After Haploidentical Stem Cell Transplantation Active, not recruiting NCT00710892 Phase 1
6 Pilot Study of Unrelated Donor Hematopoietic Stem Cell Transplantation in Patients With Life Threatening Hemophagocytic Disorders Unknown status NCT00006056 anti-thymocyte globulin;busulfan;cyclophosphamide;cyclosporine;etoposide;filgrastim;methotrexate
7 Clinical Outcome After Close Rectal Ileo Pouch Anal Anastomosis for Colitis Ulcerosa Compared to the Ileo Neo Rectal Anastomosis and the Ileo Pouch Anal Anastomosis Unknown status NCT01111708
8 Genetic Studies of the X-Linked Lymphoproliferative Disease Completed NCT00359411
9 A Randomized Trial Comparing Outcomes for the LigaSure and Disposable Stapling Instruments for Laparoscopic Surgery Completed NCT00487409
10 Randomized Controlled Trial Comparing the Utility of an Ultrasonic Coagulating Device (UCSD) With Electrothermal Bipolar Vessel Sealer (EBVS) in Thyroid Surgery. Completed NCT01765686
11 Response to Endobronchial Valves in Moderate Obstructive Airways Disease and Exercise Limitation - The REMODEL Trial Completed NCT01969734
12 Screening for Immunodeficiency Diseases in Patients With Severe Epstein-Barr Virus Infection Recruiting NCT03374566
13 Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies Terminated NCT00006054 anti-thymocyte globulin;busulfan;cyclophosphamide;cyclosporine;etoposide;methotrexate;methylprednisolone;prednisone

Search NIH Clinical Center for Lymphoproliferative Syndrome, X-Linked, 1

Genetic Tests for Lymphoproliferative Syndrome, X-Linked, 1

Genetic tests related to Lymphoproliferative Syndrome, X-Linked, 1:

# Genetic test Affiliating Genes
1 Lymphoproliferative Syndrome 1, X-Linked 29 SH2D1A XIAP

Anatomical Context for Lymphoproliferative Syndrome, X-Linked, 1

MalaCards organs/tissues related to Lymphoproliferative Syndrome, X-Linked, 1:

40
T Cells, B Cells, Kidney, Liver, Heart, Bone, Spleen

Publications for Lymphoproliferative Syndrome, X-Linked, 1

Articles related to Lymphoproliferative Syndrome, X-Linked, 1:

(show top 50) (show all 148)
# Title Authors PMID Year
1
XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome. 24 56 6
17080092 2006
2
X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease. 61 24 56
20926771 2011
3
Epstein-Barr virus-negative boys with non-Hodgkin lymphoma are mutated in the SH2D1A gene, as are patients with X-linked lymphoproliferative disease (XLP). 56 6
10556288 1999
4
Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene. 56 6
9771704 1998
5
Restimulation-induced apoptosis of T cells is impaired in patients with X-linked lymphoproliferative disease caused by SAP deficiency. 24 56
19759517 2009
6
Lymphoproliferative Disease, X-Linked 61 6
20301580 2004
7
Symptomatic males and female carriers in a large Caucasian kindred with XIAP deficiency. 6
25943627 2015
8
Dysgammaglobulinemia Associated With Glu349del, a Hypomorphic XIAP Mutation. 6
26182687 2015
9
Clinical flow cytometric screening of SAP and XIAP expression accurately identifies patients with SH2D1A and XIAP/BIRC4 mutations. 61 24
24616127 2014
10
Intronic SH2D1A mutation with impaired SAP expression and agammaglobulinemia. 6
23280491 2013
11
Clinical and genetic characteristics of XIAP deficiency in Japan. 6
22228567 2012
12
Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. 6
21173700 2011
13
X-linked lymphoproliferative syndromes: brothers or distant cousins? 61 24
20660790 2010
14
Limbic encephalitis as presentation of a SAP deficiency. 56
17620557 2007
15
Selective generation of functional somatically mutated IgM+CD27+, but not Ig isotype-switched, memory B cells in X-linked lymphoproliferative disease. 56
16424938 2006
16
Impaired humoral immunity in X-linked lymphoproliferative disease is associated with defective IL-10 production by CD4+ T cells. 56
15761493 2005
17
Regulation of NKT cell development by SAP, the protein defective in XLP. 56
15711562 2005
18
Lymphocytic vasculitis in X-linked lymphoproliferative disease. 56
11133747 2001
19
Defective NK cell activation in X-linked lymphoproliferative disease. 6
11034354 2000
20
X-linked lymphoproliferative disease. 2B4 molecules displaying inhibitory rather than activating function are responsible for the inability of natural killer cells to kill Epstein-Barr virus-infected cells. 6
10934222 2000
21
Structural basis for SH2D1A mutations in X-linked lymphoproliferative disease. 6
10694488 2000
22
Recurrent B-cell non-Hodgkin's lymphoma in two brothers with X-linked lymphoproliferative disease without evidence for Epstein-Barr virus infection. 6
10691868 2000
23
The molecular genetics of X-linked lymphoproliferative (Duncan's) disease. 56
10198724 1999
24
X linked lymphoproliferative disease in a United Kingdom family. 56
9771253 1998
25
X-linked lymphoproliferative disease: twenty-five years after the discovery. 56
8559596 1995
26
Brief report: correction of X-linked lymphoproliferative disease by transplantation of cord-blood stem cells. 56
8232431 1993
27
Correction of Duncan's syndrome by allogeneic bone marrow transplantation. 56
8102723 1993
28
Evaluation of families wherein a single male manifests a phenotype of X-linked lymphoproliferative disease (XLP). 56
8256804 1993
29
Characterization of three overlapping deletions causing X-linked lymphoproliferative disease. 56
8387453 1993
30
First prenatal diagnosis of X-linked lymphoproliferative disease. 56
1355632 1992
31
X-linked lymphoproliferative disease: prenatal detection of an unaffected histocompatible male. 56
1358486 1992
32
Methods of detection of new families with X-linked lymphoproliferative disease. 56
1847089 1991
33
Partial Xq25 deletion in a family with the X-linked lymphoproliferative disease (XLP) 56
1972651 1990
34
Mapping the mutation causing the X-linked lymphoproliferative syndrome in relation to restriction fragment length polymorphisms on Xq. 56
2567695 1989
35
Linkage analysis of seven kindreds with the X-linked lymphoproliferative syndrome (XLP) confirms that the XLP locus is near DXS42 and DXS37. 56
2567696 1989
36
X-linked lymphoproliferative syndrome. Identification of a large family in Switzerland. 56
3348254 1988
37
X-linked lymphoproliferative disease: linkage studies using DNA probes. 56
2896078 1988
38
X-linked lymphoproliferative disease: a karyotype analysis. 56
2833379 1988
39
RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression. 6
3658675 1987
40
Mapping the X-linked lymphoproliferative syndrome. 56
2882515 1987
41
Necrotizing lymphoid vasculitis in X-linked lymphoproliferative syndrome. 56
2986573 1985
42
X-linked lymphoproliferative syndrome. A new kindred with variable phenotypic expression. 56
3883747 1985
43
X-linked lymphoproliferative syndrome. Natural history of the immunodeficiency. 56
6306053 1983
44
X-linked factor in acquired immunodeficiency syndrome? 56
6132113 1983
45
Epstein-Barr virus-induced diseases in boys with the X-linked lymphoproliferative syndrome (XLP): update on studies of the registry. 56
6283885 1982
46
The American Burkitt's Lymphoma Registry: eight years' experience. 56
7059918 1982
47
X-linked lymphoproliferative syndrome. An immunodeficiency disorder with acquired agammaglobulinemia, fatal infectious mononucleosis, or malignant lymphoma. 56
6894075 1981
48
Deficient natural killer cell activity in x-linked lymphoproliferative syndrome. 56
6158759 1980
49
X-linked lymphoproliferative syndrome registry report. 56
7188959 1980
50
Epstein-Barr virus infections in the X-linked recessive lymphoproliferative syndrome. 56
85816 1978

Variations for Lymphoproliferative Syndrome, X-Linked, 1

ClinVar genetic disease variations for Lymphoproliferative Syndrome, X-Linked, 1:

6 (show all 23) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SH2D1A NM_002351.4(SH2D1A):c.163C>T (p.Arg55Ter)SNV Pathogenic 10898 rs111033623 X:123499636-123499636 X:124365786-124365786
2 SH2D1A NM_002351.4(SH2D1A):c.172C>T (p.Gln58Ter)SNV Pathogenic 10899 rs111033628 X:123499645-123499645 X:124365795-124365795
3 SH2D1A SH2D1A, 159-BP DELdeletion Pathogenic 10900
4 SH2D1A NM_002351.4(SH2D1A):c.95G>C (p.Arg32Thr)SNV Pathogenic 10901 rs111033624 X:123480587-123480587 X:124346737-124346737
5 SH2D1A NM_002351.4(SH2D1A):c.138-1G>TSNV Pathogenic 10902 X:123499610-123499610 X:124365760-124365760
6 SH2D1A NM_002351.4(SH2D1A):c.385T>A (p.Ter129Arg)SNV Pathogenic 10903 rs111033625 X:123505239-123505239 X:124371389-124371389
7 SH2D1A NM_002351.4(SH2D1A):c.302C>T (p.Pro101Leu)SNV Pathogenic 10904 rs111033626 X:123504126-123504126 X:124370276-124370276
8 SH2D1A NM_002351.4(SH2D1A):c.203C>T (p.Thr68Ile)SNV Pathogenic 10905 rs111033627 X:123504027-123504027 X:124370177-124370177
9 SH2D1A NM_002351.4(SH2D1A):c.-10C>TSNV Pathogenic 10906 X:123480483-123480483 X:124346633-124346633
10 SH2D1A SH2D1A, EX1DELdeletion Pathogenic 10907
11 SH2D1A NM_002351.4(SH2D1A):c.3G>T (p.Met1Ile)SNV Pathogenic 10908 rs111033629 X:123480495-123480495 X:124346645-124346645
12 SH2D1A SH2D1A, 163C-TSNV Pathogenic 10909
13 SH2D1A NM_002351.4(SH2D1A):c.164G>T (p.Arg55Leu)SNV Pathogenic 10910 rs111033630 X:123499637-123499637 X:124365787-124365787
14 SH2D1A NM_002351.4(SH2D1A):c.137+5G>CSNV Pathogenic 65388 rs587777612 X:123480634-123480634 X:124346784-124346784
15 SH2D1A NM_002351.4(SH2D1A):c.192G>A (p.Trp64Ter)SNV Pathogenic 547772 rs1556620706 X:123499665-123499665 X:124365815-124365815
16 SH2D1A NC_000023.10:g.(?_123480147)_(123505261_?)deldeletion Pathogenic 583520 X:123480147-123505261 X:124346297-124371411
17 SH2D1A NC_000023.10:g.(?_123499591)_(123505261_?)deldeletion Pathogenic 584122 X:123499591-123505261 X:124365741-124371411
18 SH2D1A NM_002351.4(SH2D1A):c.20A>G (p.Tyr7Cys)SNV Pathogenic 633415 rs1569527111 X:123480512-123480512 X:124346662-124346662
19 SH2D1A NM_002351.4(SH2D1A):c.385T>C (p.Ter129Arg)SNV Likely pathogenic 547773 rs111033625 X:123505239-123505239 X:124371389-124371389
20 SH2D1A NM_002351.4(SH2D1A):c.138-3C>GSNV Likely pathogenic 548931 rs1556620697 X:123499608-123499608 X:124365758-124365758
21 SH2D1A NM_002351.4(SH2D1A):c.5A>G (p.Asp2Gly)SNV Likely pathogenic 547771 rs1556619319 X:123480497-123480497 X:124346647-124346647
22 XIAP NM_001167.3(XIAP):c.844G>A (p.Glu282Lys)SNV Uncertain significance 287381 rs777303823 X:123020356-123020356 X:123886506-123886506
23 SH2D1A NM_002351.4(SH2D1A):c.116G>T (p.Gly39Val)SNV Uncertain significance 536456 rs1556619338 X:123480608-123480608 X:124346758-124346758

UniProtKB/Swiss-Prot genetic disease variations for Lymphoproliferative Syndrome, X-Linked, 1:

73 (show all 19)
# Symbol AA change Variation ID SNP ID
1 SH2D1A p.Arg32Thr VAR_005612 rs111033624
2 SH2D1A p.Thr68Ile VAR_005613 rs111033627
3 SH2D1A p.Pro101Leu VAR_005614 rs111033626
4 SH2D1A p.Arg55Leu VAR_018307 rs111033630
5 SH2D1A p.Tyr7Cys VAR_048005
6 SH2D1A p.His8Asp VAR_048006
7 SH2D1A p.Gly16Asp VAR_048007
8 SH2D1A p.Gly27Ser VAR_048008
9 SH2D1A p.Ser28Arg VAR_048009
10 SH2D1A p.Leu31Pro VAR_048010
11 SH2D1A p.Asp33Tyr VAR_048011
12 SH2D1A p.Cys42Trp VAR_048012
13 SH2D1A p.Gly49Val VAR_048013
14 SH2D1A p.Thr53Ile VAR_048014
15 SH2D1A p.Tyr54Cys VAR_048015
16 SH2D1A p.Ile84Thr VAR_048017
17 SH2D1A p.Phe87Ser VAR_048018
18 SH2D1A p.Gln99Pro VAR_048019
19 SH2D1A p.Val102Gly VAR_048020

Expression for Lymphoproliferative Syndrome, X-Linked, 1

Search GEO for disease gene expression data for Lymphoproliferative Syndrome, X-Linked, 1.

Pathways for Lymphoproliferative Syndrome, X-Linked, 1

Pathways related to Lymphoproliferative Syndrome, X-Linked, 1 according to KEGG:

36
# Name Kegg Source Accession
1 Natural killer cell mediated cytotoxicity hsa04650
2 Apoptosis hsa04210

GO Terms for Lymphoproliferative Syndrome, X-Linked, 1

Cellular components related to Lymphoproliferative Syndrome, X-Linked, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 exocytic vesicle GO:0070382 9.16 UNC13D RAB27A
2 cytolytic granule GO:0044194 8.96 STXBP2 PRF1
3 Weibel-Palade body GO:0033093 8.62 UNC13D RAB27A

Biological processes related to Lymphoproliferative Syndrome, X-Linked, 1 according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 neutrophil degranulation GO:0043312 9.89 UNC13D TOLLIP STXBP2 RAB27A MAGT1
2 vesicle-mediated transport GO:0016192 9.83 STXBP2 STX11 RAB27A AP3B1
3 leukocyte migration GO:0050900 9.76 PTPN11 CD84 CD48 CD244
4 adaptive immune response GO:0002250 9.63 SLAMF7 SLAMF1 SH2D1A ITK CD84 CD244
5 positive regulation of exocytosis GO:0045921 9.57 UNC13D RAB27A
6 positive regulation of natural killer cell mediated cytotoxicity GO:0045954 9.56 SLAMF6 SH2D1A
7 exocytosis GO:0006887 9.56 UNC13D STXBP2 STX11 RAB27A
8 immune system process GO:0002376 9.56 SLAMF7 SLAMF6 SLAMF1 SH2D1A LY9 ITK
9 natural killer cell mediated cytotoxicity GO:0042267 9.55 SLAMF7 LYST
10 melanosome organization GO:0032438 9.54 LYST AP3B1
11 cellular defense response GO:0006968 9.54 SH2D1A PRF1 ITK
12 positive regulation of interleukin-17 production GO:0032740 9.51 SLAMF6 LY9
13 regulation of mast cell degranulation GO:0043304 9.48 UNC13D STXBP2
14 T-helper 17 cell lineage commitment GO:0072540 9.43 SLAMF6 LY9
15 natural killer cell degranulation GO:0043320 9.4 UNC13D RAB27A
16 positive regulation of regulated secretory pathway GO:1903307 9.32 UNC13D RAB27A
17 innate immune response GO:0045087 9.23 TOLLIP SLAMF7 SLAMF6 SLAMF1 SH2D1A LY9

Sources for Lymphoproliferative Syndrome, X-Linked, 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
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68 SNOMED-CT via HPO
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70 Tocris
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72 UMLS via Orphanet
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