LPFS2
MCID: LYM107
MIFTS: 44

Lymphoproliferative Syndrome 2 (LPFS2)

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

Aliases & Classifications for Lymphoproliferative Syndrome 2

MalaCards integrated aliases for Lymphoproliferative Syndrome 2:

Name: Lymphoproliferative Syndrome 2 56 12 73 29 13 6 15 39 71
Cd27 Deficiency 56 12 58 73
Lpfs2 56 12 73
Autosomal Recessive Lymphoproliferative Disease Due to Cd27 Deficiency 58
Combined Immunodeficiency Due to Cd27 Deficiency 58

Characteristics:

Orphanet epidemiological data:

58
combined immunodeficiency due to cd27 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset in first months or years of life
variable survival
recurrent acute episodes
favorable response to rituxan (in some patients)


HPO:

31
lymphoproliferative syndrome 2:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity


Classifications:

Orphanet: 58  
Rare immunological diseases


External Ids:

Disease Ontology 12 DOID:0060708
OMIM 56 615122
OMIM Phenotypic Series 56 PS308240
MeSH 43 D008232
ICD10 32 D47.9
ICD10 via Orphanet 33 D47.9
Orphanet 58 ORPHA238505
UMLS 71 C3554540

Summaries for Lymphoproliferative Syndrome 2

OMIM : 56 Lymphoproliferative syndrome-2, also known as CD27 deficiency, is an autosomal recessive immunodeficiency disorder associated with persistent symptomatic EBV viremia, hypogammaglobulinemia, and impairment in specific antibody function resulting from impaired T cell-dependent B-cell responses and T-cell dysfunction (summary by van Montfrans et al., 2012). The phenotype can vary significantly, from asymptomatic borderline-low hypogammaglobulinemia, to a full-blown symptomatic systemic inflammatory response with life-threatening EBV-related complications, including hemophagocytic lymphohistiocytosis, a lymphoproliferative disorder, and malignant lymphoma requiring stem cell transplantation (summary by Salzer et al., 2013). For a discussion of genetic heterogeneity of lymphoproliferative syndrome, see XLP1 (308240). (615122)

MalaCards based summary : Lymphoproliferative Syndrome 2, also known as cd27 deficiency, is related to lymphoproliferative syndrome, x-linked, 2 and immune deficiency disease, and has symptoms including fever An important gene associated with Lymphoproliferative Syndrome 2 is CD27 (CD27 Molecule), and among its related pathways/superpathways are Innate Immune System and Akt Signaling. Affiliated tissues include t cells, b cells and bone marrow, and related phenotypes are ascites and aplastic anemia

Disease Ontology : 12 A lymphoproliferative syndrome characterized by autosomal recessive inheritance, persistent symptomatic Epstein-Barr virus-associated viremia, hypogammaglobulinemia, and impairment in specific antibody function and that has material basis in homozygous mutation in the CD27 gene on chromosome 12p13.

UniProtKB/Swiss-Prot : 73 Lymphoproliferative syndrome 2: An autosomal recessive immunodeficiency disorder associated with persistent symptomatic EBV viremia, hypogammaglobulinemia, and impaired T-cell-dependent B-cell responses and T-cell dysfunction. The phenotype is highly variable, ranging from asymptomatic borderline-low hypogammaglobulinemia, to a full-blown symptomatic systemic inflammatory response with life-threatening EBV-related complications, including hemophagocytic lymphohistiocytosis, a lymphoproliferative disorder, and malignant lymphoma requiring stem cell transplantation.

Related Diseases for Lymphoproliferative Syndrome 2

Diseases in the Lymphoproliferative Syndrome family:

Autoimmune Lymphoproliferative Syndrome Autoimmune Lymphoproliferative Syndrome, Type Iia
Lymphoproliferative Syndrome 1 Lymphoproliferative Syndrome 2
Autoimmune Lymphoproliferative Syndrome, Type Iii Autoimmune Lymphoproliferative Syndrome, Type V
Lymphoproliferative Syndrome 3

Diseases related to Lymphoproliferative Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 50)
# Related Disease Score Top Affiliating Genes
1 lymphoproliferative syndrome, x-linked, 2 31.0 XIAP STXBP2 SLAMF1 SH2D1A ITK
2 immune deficiency disease 29.2 TNFRSF13B SLAMF1 SH2D1A CD27
3 hemophagocytic lymphohistiocytosis 28.8 XIAP STXBP2 SH2D1A ITK CD27
4 lymphoproliferative syndrome, x-linked, 1 27.6 XIAP STXBP2 SLAMF1 SH2D1A MAGT1 ITK
5 janus kinase-3 deficiency 10.2 STK4 MAGT1
6 transient hypogammaglobulinemia of infancy 10.2 TNFRSF13B CD27
7 mixed oligodendroglioma-astrocytoma 10.2 TNFRSF4 ITK
8 oral hairy leukoplakia 10.1 SH2D1A CD8A
9 immunodeficiency 19 10.1 SH2D1A CD8A
10 macroglobulinemia 10.0 TNFRSF13B CD70 CD27
11 cone-rod dystrophy 1 10.0 TNFRSF4 TNFRSF13B
12 cd40 ligand deficiency 10.0 TNFRSF13B SH2D1A CD27
13 t cell deficiency 10.0 MAGT1 CD8A CD27
14 acute myocarditis 10.0 CD8A CD70
15 good syndrome 10.0 TNFRSF13B CD8A
16 immunodeficiency with hyper-igm, type 3 9.9 TNFRSF13B CD8A
17 lymphoma, hodgkin, classic 9.9
18 immunodysregulation, polyendocrinopathy, and enteropathy, x-linked 9.9
19 aplastic anemia 9.9
20 pulmonary fibrosis and/or bone marrow failure, telomere-related, 2 9.9
21 bacterial sepsis 9.9
22 uveitis 9.9
23 agammaglobulinemia 9.9
24 combined t cell and b cell immunodeficiency 9.9
25 thrombocytopenia due to platelet alloimmunization 9.9 TNFRSF13B CD8A
26 macs syndrome 9.9 SLAMF1 CD8A
27 immunoglobulin alpha deficiency 9.8 TNFRSF13B CD8A CD27
28 chickenpox 9.8 CD8A CD27
29 cryptococcal meningitis 9.8 TNFRSF13B CD8A
30 lymphopenia 9.7 PIK3CD MAGT1 ITK
31 herpangina 9.7 SLAMF1 CD8A
32 autoimmune lymphoproliferative syndrome 9.7 SH2D1A MAGT1 CD8A CD27
33 lymphoma 9.7 XIAP SH2D1A ITK CD70 CD27
34 cowpox 9.7 XIAP CD8A
35 pfeiffer syndrome 9.7 SLAMF1 SH2D1A CD8A
36 common variable immunodeficiency 9.6 XIAP TNFRSF13B SH2D1A CD70 CD27
37 lymphoproliferative syndrome 1 9.5 XIAP STXBP2 SH2D1A ITK
38 lymphatic system disease 9.5 STXBP2 SH2D1A CD8A
39 b cell deficiency 9.4 TNFRSF13B SH2D1A ITK CD8A CD27
40 cone-rod dystrophy 2 9.4 TNFRSF4 TNFRSF13B CD8A CD27
41 lymphoproliferative syndrome 9.3 XIAP SLAMF1 SH2D1A ITK CD70 CD27
42 coronin-1a deficiency 9.3 STK4 SH2D1A PIK3CD MAGT1 ITK
43 immunodeficiency, x-linked, with magnesium defect, epstein-barr virus infection, and neoplasia 9.3 SH2D1A MAGT1 ITK CD8A CD70 CD27
44 myeloma, multiple 9.2 XIAP TNFRSF13B SLAMF1 CD8A CD27
45 lymphoma, non-hodgkin, familial 9.2 XIAP TNFRSF13B SH2D1A CD8A CD70 CD27
46 pancytopenia 9.1 XIAP STXBP2 SH2D1A ITK CD8A
47 leukemia, chronic lymphocytic 9.0 XIAP TNFRSF13B PIK3CD CD8A CD70 CD27
48 systemic lupus erythematosus 8.8 TNFRSF4 TNFRSF13B SLAMF1 CD8A CD70 CD27
49 dysgammaglobulinemia 8.8 XIAP TNFRSF13B STXBP2 SLAMF1 SH2D1A MAGT1
50 selective immunoglobulin deficiency disease 8.4 XIAP TNFRSF13B STXBP2 SLAMF1 SH2D1A MAGT1

Graphical network of the top 20 diseases related to Lymphoproliferative Syndrome 2:



Diseases related to Lymphoproliferative Syndrome 2

Symptoms & Phenotypes for Lymphoproliferative Syndrome 2

Human phenotypes related to Lymphoproliferative Syndrome 2:

31 (show all 11)
# Description HPO Frequency HPO Source Accession
1 ascites 31 occasional (7.5%) HP:0001541
2 aplastic anemia 31 occasional (7.5%) HP:0001915
3 lymphoma 31 occasional (7.5%) HP:0002665
4 lymphoproliferative disorder 31 occasional (7.5%) HP:0005523
5 hemophagocytosis 31 occasional (7.5%) HP:0012156
6 splenomegaly 31 HP:0001744
7 hepatomegaly 31 HP:0002240
8 fever 31 HP:0001945
9 decreased antibody level in blood 31 HP:0004313
10 lymphadenopathy 31 HP:0002716
11 persistent ebv viremia 31 HP:0020072

Symptoms via clinical synopsis from OMIM:

56
Abdomen Spleen:
splenomegaly

Metabolic Features:
fever

Laboratory Abnormalities:
persistent ebv viremia
increased susceptibility to ebv infection
decreased fibrinogen (in some patients)

Hematology:
pancytopenia (in some patients)
aplastic anemia (in some patients)

Abdomen Liver:
hepatomegaly

Immunology:
lymphadenopathy
hypogammaglobulinemia
decreased t cell-dependent antibody production
defective cd8+ t cell function
lack of cd27 expression on lymphocytes
more
Muscle Soft Tissue:
ascites (in some patients)

Neoplasia:
hemophagocytic lymphohistiocytosis (in some patients)
lymphoproliferative disorder (in some patients)
lymphoma (in some patients)

Clinical features from OMIM:

615122

UMLS symptoms related to Lymphoproliferative Syndrome 2:


fever

MGI Mouse Phenotypes related to Lymphoproliferative Syndrome 2:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.77 CD27 CD70 CD8A ITK MAGT1 PIK3CD
2 immune system MP:0005387 9.44 CD27 CD70 CD8A ITK MAGT1 PIK3CD

Drugs & Therapeutics for Lymphoproliferative Syndrome 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Screening for Immunodeficiency Diseases in Patients With Severe Epstein-Barr Virus Infection Recruiting NCT03374566

Search NIH Clinical Center for Lymphoproliferative Syndrome 2

Genetic Tests for Lymphoproliferative Syndrome 2

Genetic tests related to Lymphoproliferative Syndrome 2:

# Genetic test Affiliating Genes
1 Lymphoproliferative Syndrome 2 29 CD27

Anatomical Context for Lymphoproliferative Syndrome 2

MalaCards organs/tissues related to Lymphoproliferative Syndrome 2:

40
T Cells, B Cells, Bone Marrow, Bone

Publications for Lymphoproliferative Syndrome 2

Articles related to Lymphoproliferative Syndrome 2:

# Title Authors PMID Year
1
Combined immunodeficiency with life-threatening EBV-associated lymphoproliferative disorder in patients lacking functional CD27. 56 6
22801960 2013
2
CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia. 56 6
22197273 2012
3
Loss-of-function mutations within the IL-2 inducible kinase ITK in patients with EBV-associated lymphoproliferative diseases. 6
22289921 2012
4
CD27: a new player in the field of common variable immunodeficiency and EBV-associated lymphoproliferative disorder? 56
22365582 2012
5
IL-2-inducible T-cell kinase deficiency: clinical presentation and therapeutic approach. 6
21109689 2011
6
Girls homozygous for an IL-2-inducible T cell kinase mutation that leads to protein deficiency develop fatal EBV-associated lymphoproliferation. 6
19425169 2009
7
Unique BIR domain sets determine inhibitor of apoptosis protein-driven cell death and NOD2 complex signal specificity. 61
30018081 2018
8
Nucleotide-binding oligomerization domain (NOD) signaling defects and cell death susceptibility cannot be uncoupled in X-linked inhibitor of apoptosis (XIAP)-driven inflammatory disease. 61
28404814 2017
9
Human X-linked variable immunodeficiency caused by a hypomorphic mutation in XIAP in association with a rare polymorphism in CD40LG. 61
21543760 2011
10
Unrelated cord blood transplantation for severe combined immunodeficiency and other primary immunodeficiencies. 61
18084339 2008

Variations for Lymphoproliferative Syndrome 2

ClinVar genetic disease variations for Lymphoproliferative Syndrome 2:

6 (show all 17) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CD27 NM_001242.4(CD27):c.541C>T (p.Gln181Ter)SNV Pathogenic 540910 rs779092602 12:6560063-6560063 12:6450897-6450897
2 CD27 NM_001242.4(CD27):c.239dup (p.His80fs)duplication Pathogenic 578414 rs748418658 12:6554691-6554692 12:6445525-6445526
3 CD27 NM_001242.4(CD27):c.24G>A (p.Trp8Ter)SNV Pathogenic 40889 rs398122933 12:6554285-6554285 12:6445119-6445119
4 CD27 NM_001242.4(CD27):c.158G>A (p.Cys53Tyr)SNV Pathogenic 40890 rs397514667 12:6554611-6554611 12:6445445-6445445
5 CD27 NM_001242.4(CD27):c.635A>G (p.His212Arg)SNV Uncertain significance 540909 rs755699729 12:6560157-6560157 12:6450991-6450991
6 CD27 NM_001242.4(CD27):c.122A>G (p.Gln41Arg)SNV Uncertain significance 581569 rs752259578 12:6554383-6554383 12:6445217-6445217
7 CD27 NM_001242.4(CD27):c.277G>A (p.Val93Ile)SNV Uncertain significance 575563 rs761113232 12:6559347-6559347 12:6450181-6450181
8 CD27 NM_001242.4(CD27):c.7C>T (p.Arg3Trp)SNV Uncertain significance 663095 12:6554268-6554268 12:6445102-6445102
9 CD27 NM_001242.4(CD27):c.206T>C (p.Val69Ala)SNV Uncertain significance 655342 12:6554659-6554659 12:6445493-6445493
10 CD27 NM_001242.4(CD27):c.233G>A (p.Arg78Gln)SNV Uncertain significance 649825 12:6554686-6554686 12:6445520-6445520
11 CD27 NM_001242.4(CD27):c.254G>A (p.Arg85Gln)SNV Uncertain significance 666185 12:6554707-6554707 12:6445541-6445541
12 CD27 NM_001242.4(CD27):c.353C>A (p.Thr118Asn)SNV Uncertain significance 644090 12:6559423-6559423 12:6450257-6450257
13 CD27 NM_001242.4(CD27):c.488T>C (p.Leu163Pro)SNV Uncertain significance 656369 12:6559746-6559746 12:6450580-6450580
14 CD27 NM_001242.4(CD27):c.546A>T (p.Arg182Ser)SNV Uncertain significance 663562 12:6560068-6560068 12:6450902-6450902
15 CD27 NM_001242.4(CD27):c.712A>G (p.Arg238Gly)SNV Uncertain significance 662511 12:6560487-6560487 12:6451321-6451321
16 CD27 NM_001242.4(CD27):c.721G>A (p.Glu241Lys)SNV Uncertain significance 656240 12:6560496-6560496 12:6451330-6451330
17 CD27 NM_001242.4(CD27):c.225C>T (p.His75=)SNV Likely benign 473870 rs745713273 12:6554678-6554678 12:6445512-6445512

UniProtKB/Swiss-Prot genetic disease variations for Lymphoproliferative Syndrome 2:

73
# Symbol AA change Variation ID SNP ID
1 CD27 p.Cys53Tyr VAR_069793 rs397514667

Expression for Lymphoproliferative Syndrome 2

Search GEO for disease gene expression data for Lymphoproliferative Syndrome 2.

Pathways for Lymphoproliferative Syndrome 2

Pathways related to Lymphoproliferative Syndrome 2 according to GeneCards Suite gene sharing:

(show all 11)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.65 TNFRSF4 TNFRSF13B SH2D1A PIK3CD MAGT1 ITK
2
Show member pathways
13.06 XIAP TNFRSF4 TNFRSF13B ITK CD70 CD27
3
Show member pathways
12.46 XIAP PIK3CD CD70 CD27
4
Show member pathways
12.2 TNFRSF4 TNFRSF13B CD70 CD27
5 12.14 TNFRSF4 SH2D1A ITK CD8A
6
Show member pathways
11.3 XIAP TNFRSF4 TNFRSF13B
7 11.1 SLAMF1 CD70 CD27
8 11.07 TNFRSF13B CD8A
9 10.97 ITK CD8A
10 10.86 TNFRSF13B SLAMF1 CD27
11 10.4 TNFRSF4 TNFRSF13B CD70 CD27

GO Terms for Lymphoproliferative Syndrome 2

Cellular components related to Lymphoproliferative Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of plasma membrane GO:0005887 9.1 TNFRSF4 TNFRSF13B MAGT1 CD8A CD70 CD27

Biological processes related to Lymphoproliferative Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 adaptive immune response GO:0002250 9.55 TNFRSF13B SLAMF1 SH2D1A PIK3CD ITK
2 T cell activation GO:0042110 9.43 PIK3CD ITK CD8A
3 immune system process GO:0002376 9.43 TNFRSF13B SLAMF1 SH2D1A PIK3CD ITK CD8A
4 cytokine production GO:0001816 9.37 PIK3CD ITK
5 T cell mediated immunity GO:0002456 9.32 CD8A CD70
6 tumor necrosis factor-mediated signaling pathway GO:0033209 8.92 TNFRSF4 TNFRSF13B CD70 CD27

Molecular functions related to Lymphoproliferative Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cysteine-type endopeptidase inhibitor activity involved in apoptotic process GO:0043027 8.62 XIAP CD27

Sources for Lymphoproliferative Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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