LPFS2
MCID: LYM107
MIFTS: 41

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 57 12 74 29 13 6 15 40 72
Cd27 Deficiency 57 12 59 74
Lpfs2 57 12 74
Autosomal Recessive Lymphoproliferative Disease Due to Cd27 Deficiency 59
Combined Immunodeficiency Due to Cd27 Deficiency 59

Characteristics:

Orphanet epidemiological data:

59
combined immunodeficiency due to cd27 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

57
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:

32
lymphoproliferative syndrome 2:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity


Classifications:

Orphanet: 59  
Rare immunological diseases


External Ids:

Disease Ontology 12 DOID:0060708
MeSH 44 D008232
ICD10 33 D47.9
ICD10 via Orphanet 34 D47.9
Orphanet 59 ORPHA238505
UMLS 72 C3554540

Summaries for Lymphoproliferative Syndrome 2

OMIM : 57 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 hemophagocytic lymphohistiocytosis and lymphoproliferative syndrome, x-linked, 2, and has symptoms including fever An important gene associated with Lymphoproliferative Syndrome 2 is CD27 (CD27 Molecule), and among its related pathways/superpathways are Development Angiotensin activation of ERK and TRAF Pathway. Affiliated tissues include t cells and b cells, 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 : 74 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

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:

32 (show all 11)
# Description HPO Frequency HPO Source Accession
1 ascites 32 occasional (7.5%) HP:0001541
2 aplastic anemia 32 occasional (7.5%) HP:0001915
3 lymphoma 32 occasional (7.5%) HP:0002665
4 lymphoproliferative disorder 32 occasional (7.5%) HP:0005523
5 hemophagocytosis 32 occasional (7.5%) HP:0012156
6 splenomegaly 32 HP:0001744
7 hepatomegaly 32 HP:0002240
8 fever 32 HP:0001945
9 decreased antibody level in blood 32 HP:0004313
10 lymphadenopathy 32 HP:0002716
11 persistent ebv viremia 32 HP:0020072

Symptoms via clinical synopsis from OMIM:

57
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:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.35 CD27 CD70 MAGT1 PIK3CD XIAP
2 immune system MP:0005387 9.02 CD27 CD70 MAGT1 PIK3CD XIAP

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:

41
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. 8 71
22801960 2013
2
CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia. 8 71
22197273 2012
3
Loss-of-function mutations within the IL-2 inducible kinase ITK in patients with EBV-associated lymphoproliferative diseases. 71
22289921 2012
4
CD27: a new player in the field of common variable immunodeficiency and EBV-associated lymphoproliferative disorder? 8
22365582 2012
5
IL-2-inducible T-cell kinase deficiency: clinical presentation and therapeutic approach. 71
21109689 2011
6
Girls homozygous for an IL-2-inducible T cell kinase mutation that leads to protein deficiency develop fatal EBV-associated lymphoproliferation. 71
19425169 2009
7
Unique BIR domain sets determine inhibitor of apoptosis protein-driven cell death and NOD2 complex signal specificity. 38
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. 38
28404814 2017
9
Human X-linked variable immunodeficiency caused by a hypomorphic mutation in XIAP in association with a rare polymorphism in CD40LG. 38
21543760 2011
10
Unrelated cord blood transplantation for severe combined immunodeficiency and other primary immunodeficiencies. 38
18084339 2008

Variations for Lymphoproliferative Syndrome 2

ClinVar genetic disease variations for Lymphoproliferative Syndrome 2:

6 (show all 22)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 CD27 NM_001242.4(CD27): c.541C> T (p.Gln181Ter) single nucleotide variant Pathogenic rs779092602 12:6560063-6560063 12:6450897-6450897
2 CD27 NM_001242.4(CD27): c.24G> A (p.Trp8Ter) single nucleotide variant Pathogenic rs398122933 12:6554285-6554285 12:6445119-6445119
3 CD27 NM_001242.4(CD27): c.158G> A (p.Cys53Tyr) single nucleotide variant Pathogenic rs397514667 12:6554611-6554611 12:6445445-6445445
4 CD27 NM_001242.4(CD27): c.239dup (p.His80fs) duplication Pathogenic 12:6554692-6554692 12:6445526-6445526
5 CD27 NM_001242.4(CD27): c.122A> G (p.Gln41Arg) single nucleotide variant Uncertain significance 12:6554383-6554383 12:6445217-6445217
6 CD27 NM_001242.4(CD27): c.277G> A (p.Val93Ile) single nucleotide variant Uncertain significance 12:6559347-6559347 12:6450181-6450181
7 CD27 NM_001242.4(CD27): c.7C> T (p.Arg3Trp) single nucleotide variant Uncertain significance 12:6554268-6554268 12:6445102-6445102
8 CD27 NM_001242.4(CD27): c.206T> C (p.Val69Ala) single nucleotide variant Uncertain significance 12:6554659-6554659 12:6445493-6445493
9 CD27 NM_001242.4(CD27): c.233G> A (p.Arg78Gln) single nucleotide variant Uncertain significance 12:6554686-6554686 12:6445520-6445520
10 CD27 NM_001242.4(CD27): c.254G> A (p.Arg85Gln) single nucleotide variant Uncertain significance 12:6554707-6554707 12:6445541-6445541
11 CD27 NM_001242.4(CD27): c.353C> A (p.Thr118Asn) single nucleotide variant Uncertain significance 12:6559423-6559423 12:6450257-6450257
12 CD27 NM_001242.4(CD27): c.488T> C (p.Leu163Pro) single nucleotide variant Uncertain significance 12:6559746-6559746 12:6450580-6450580
13 CD27 NM_001242.4(CD27): c.546A> T (p.Arg182Ser) single nucleotide variant Uncertain significance 12:6560068-6560068 12:6450902-6450902
14 CD27 NM_001242.4(CD27): c.712A> G (p.Arg238Gly) single nucleotide variant Uncertain significance 12:6560487-6560487 12:6451321-6451321
15 CD27 NM_001242.4(CD27): c.721G> A (p.Glu241Lys) single nucleotide variant Uncertain significance 12:6560496-6560496 12:6451330-6451330
16 CD27 NM_001242.4(CD27): c.635A> G (p.His212Arg) single nucleotide variant Uncertain significance rs755699729 12:6560157-6560157 12:6450991-6450991
17 CD27 NM_001242.4(CD27): c.539-9C> T single nucleotide variant Likely benign rs374055287 12:6560052-6560052 12:6450886-6450886
18 CD27 NM_001242.4(CD27): c.225C> T (p.His75=) single nucleotide variant Likely benign rs745713273 12:6554678-6554678 12:6445512-6445512
19 CD27 NM_001242.4(CD27): c.495C> T (p.Asp165=) single nucleotide variant Likely benign rs375150093 12:6559753-6559753 12:6450587-6450587
20 CD27 NM_001242.4(CD27): c.30C> T (p.Cys10=) single nucleotide variant Benign rs34540052 12:6554291-6554291 12:6445125-6445125
21 CD27 NM_001242.4(CD27): c.269-9T> C single nucleotide variant Benign rs11830902 12:6559330-6559330 12:6450164-6450164
22 CD27 NM_001242.4(CD27): c.698G> A (p.Arg233His) single nucleotide variant Benign rs2532502 12:6560473-6560473 12:6451307-6451307

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

74
# 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

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 tumor necrosis factor-mediated signaling pathway GO:0033209 9.16 CD70 CD27
2 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043154 8.96 XIAP CD27
3 extrinsic apoptotic signaling pathway GO:0097191 8.62 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 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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