LPFS2
MCID: LYM107
MIFTS: 42

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 NF-kappaB Signaling and TNF Superfamily - Human Ligand-Receptor Interactions and their Associated Functions. Affiliated tissues include t cells and b cells, and related phenotypes are ascites and lymphoma

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 45)
# Related Disease Score Top Affiliating Genes
1 lymphoproliferative syndrome, x-linked, 2 30.6 XIAP STXBP2 SLAMF1 SH2D1A ITK AP3B1
2 immune deficiency disease 29.0 XIAP SLAMF1 SH2D1A CD27
3 hemophagocytic lymphohistiocytosis 28.7 XIAP STXBP2 SH2D1A ITK CD27 AP3B1
4 lymphoproliferative syndrome, x-linked, 1 27.1 XIAP STXBP2 SLAMF1 SH2D1A MAGT1 ITK
5 transient hypogammaglobulinemia of infancy 10.2 SH2D1A CD27
6 oral hairy leukoplakia 10.0 SH2D1A CD8A
7 hemophagocytic lymphohistiocytosis, familial, 2 10.0 STXBP2 SH2D1A
8 immunodeficiency with hyper-igm, type 1 10.0 SH2D1A CD27
9 immunoglobulin alpha deficiency 9.9 CD8A CD27
10 hermansky-pudlak syndrome 2 9.9 STXBP2 AP3B1
11 cd40 ligand deficiency 9.9 SH2D1A CD8A CD27
12 lymphoma, hodgkin, classic 9.9
13 immunodysregulation, polyendocrinopathy, and enteropathy, x-linked 9.9
14 aplastic anemia 9.9
15 pulmonary fibrosis and/or bone marrow failure, telomere-related, 2 9.9
16 bacterial sepsis 9.9
17 uveitis 9.9
18 agammaglobulinemia 9.9
19 mixed oligodendroglioma-astrocytoma 9.9 TNFRSF4 ITK
20 chickenpox 9.9 CD8A CD27
21 b cell deficiency 9.9 SH2D1A CD8A CD27
22 common variable immunodeficiency 9.9 XIAP SH2D1A CD70 CD27
23 t cell deficiency 9.8 CORO1A CD8A CD27
24 griscelli syndrome, type 2 9.8 STXBP2 SH2D1A AP3B1
25 griscelli syndrome 9.8 STXBP2 SH2D1A AP3B1
26 lymphoproliferative syndrome 1 9.8 XIAP STXBP2 SH2D1A ITK
27 lymphopenia 9.8 MAGT1 ITK CORO1A
28 autoimmune lymphoproliferative syndrome 9.7 SH2D1A MAGT1 CD8A CD27
29 epidermodysplasia verruciformis 1 9.7 STK4 CORO1A CD8A
30 cowpox 9.7 XIAP CD8A
31 immunodeficiency, x-linked, with magnesium defect, epstein-barr virus infection, and neoplasia 9.7 SH2D1A MAGT1 ITK CD8A
32 acute hemorrhagic encephalitis 9.7 XIAP STXBP2 SH2D1A CD8A
33 lymphoma 9.6 XIAP SH2D1A ITK CD70 CD27
34 omenn syndrome 9.5 SH2D1A MAGT1 CORO1A CD8A
35 lymphoma, non-hodgkin, familial 9.5 XIAP SH2D1A CD8A CD70 CD27
36 coronin-1a deficiency 9.4 STK4 SH2D1A MAGT1 ITK CORO1A
37 chediak-higashi syndrome 9.4 STXBP2 SH2D1A CD8A AP3B1
38 pancytopenia 9.4 XIAP STXBP2 SH2D1A ITK CD8A
39 combined t cell and b cell immunodeficiency 9.4 SH2D1A MAGT1 CORO1A CD8A CD27
40 pfeiffer syndrome 9.3 SLAMF1 SH2D1A CD8A CD27
41 myeloma, multiple 9.2 XIAP SLAMF1 CD8A CD27
42 dysgammaglobulinemia 9.1 XIAP SLAMF1 SH2D1A MAGT1 CD8A
43 lymphoproliferative syndrome 9.1 XIAP SLAMF1 SH2D1A ITK CD70 CD27
44 leukemia, chronic lymphocytic 9.0 XIAP TNFRSF4 ITK CD8A CD70 CD27
45 selective immunoglobulin deficiency disease 8.8 XIAP STXBP2 SLAMF1 SH2D1A MAGT1 CD8A

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 lymphoma 31 occasional (7.5%) HP:0002665
3 lymphoproliferative disorder 31 occasional (7.5%) HP:0005523
4 hemophagocytosis 31 occasional (7.5%) HP:0012156
5 aplastic anemia 31 occasional (7.5%) HP:0001915
6 splenomegaly 31 HP:0001744
7 hepatomegaly 31 HP:0002240
8 fever 31 HP:0001945
9 lymphadenopathy 31 HP:0002716
10 decreased circulating antibody level 31 HP:0004313
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 cellular MP:0005384 9.85 AP3B1 CD27 CD8A CORO1A ITK SH2D1A
2 hematopoietic system MP:0005397 9.77 AP3B1 CD27 CD70 CD8A CORO1A ITK
3 immune system MP:0005387 9.44 AP3B1 CD27 CD70 CD8A CORO1A ITK

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

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. 6 56
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 32) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# 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 NC_000012.12:g.6445132G>ASNV Uncertain significance 857202 12:6554298-6554298 12:6445132-6445132
18 CD27 NC_000012.12:g.6445133G>TSNV Uncertain significance 863143 12:6554299-6554299 12:6445133-6445133
19 CD27 NC_000012.12:g.6445510C>ASNV Uncertain significance 863157 12:6554676-6554676 12:6445510-6445510
20 CD27 NC_000012.12:g.6450263G>ASNV Uncertain significance 839080 12:6559429-6559429 12:6450263-6450263
21 CD27 NC_000012.12:g.6450295C>TSNV Uncertain significance 847571 12:6559461-6559461 12:6450295-6450295
22 CD27 NC_000012.12:g.6450299C>TSNV Uncertain significance 842024 12:6559465-6559465 12:6450299-6450299
23 CD27 NC_000012.12:g.6450317C>TSNV Uncertain significance 860936 12:6559483-6559483 12:6450317-6450317
24 CD27 NC_000012.12:g.6450170C>TSNV Uncertain significance 851730 12:6559336-6559336 12:6450170-6450170
25 CD27 NM_001242.4(CD27):c.539-9C>TSNV Likely benign 540912 rs374055287 12:6560052-6560052 12:6450886-6450886
26 CD27 NM_001242.4(CD27):c.225C>T (p.His75=)SNV Likely benign 473870 rs745713273 12:6554678-6554678 12:6445512-6445512
27 CD27 NM_001242.4(CD27):c.495C>T (p.Asp165=)SNV Likely benign 540911 rs375150093 12:6559753-6559753 12:6450587-6450587
28 CD27 NM_001242.4(CD27):c.396G>A (p.Ser132=)SNV Likely benign 756533 12:6559466-6559466 12:6450300-6450300
29 CD27 NM_001242.4(CD27):c.30C>T (p.Cys10=)SNV Benign 473872 rs34540052 12:6554291-6554291 12:6445125-6445125
30 CD27 NM_001242.4(CD27):c.269-9T>CSNV Benign 473871 rs11830902 12:6559330-6559330 12:6450164-6450164
31 CD27 NM_001242.4(CD27):c.698G>A (p.Arg233His)SNV Benign 473873 rs2532502 12:6560473-6560473 12:6451307-6451307
32 CD27 NM_001242.4(CD27):c.539-6T>CSNV Benign 724198 12:6560055-6560055 12:6450889-6450889

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:

# Super pathways Score Top Affiliating Genes
1 11.77 TNFRSF4 SH2D1A ITK CD8A
2
Show member pathways
10.71 TNFRSF4 CD70 CD27
3 10.65 ITK CD8A

GO Terms for Lymphoproliferative Syndrome 2

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 9.46 SLAMF1 SH2D1A ITK CD8A
2 tumor necrosis factor-mediated signaling pathway GO:0033209 9.13 TNFRSF4 CD70 CD27
3 T cell mediated immunity GO:0002456 8.62 CD8A CD70

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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