MCID: GRS014
MIFTS: 49

Griscelli Syndrome, Type 2

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Skin diseases, Immune diseases, Eye diseases, Blood diseases

Aliases & Classifications for Griscelli Syndrome, Type 2

MalaCards integrated aliases for Griscelli Syndrome, Type 2:

Name: Griscelli Syndrome, Type 2 53 13 51 69
Griscelli Syndrome Type 2 12 49 28 41 14
Gs2 53 12 49 71
Hypopigmentation-Immunodeficiency with or Without Neurologic Impairment Syndrome 12 49 55
Griscelli Syndrome with Hemophagocytic Syndrome 53 12 49
Partial Albinism and Immunodeficiency Syndrome 53 12 49
Griscelli-Pruniéras Syndrome Type 2 12 49 55
Paid Syndrome 53 12 49
Griscelli Disease Type 2 55
Griscelli Syndrome 2 71

Characteristics:

Orphanet epidemiological data:

55
griscelli disease type 2
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy; Age of death: late childhood;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy or early childhood
death in childhood
multiorgan failure may result from hs
see also griscelli syndrome type 1 for a similar disorder without immunological abnormalities and griscelli syndrome type 3 for a similar disorder without neurologic or immunologic abnormalities


HPO:

31
griscelli syndrome, type 2:
Onset and clinical course infantile onset
Mortality/Aging death in childhood
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Griscelli Syndrome, Type 2

NIH Rare Diseases : 49 Griscelli syndrome type 2 (GS2) is a rare, inherited condition that affects the skin, hair, and immune system. People with GS2 have unusually light skin and silver-colored hair. They are also prone to recurrent infections and develop an immune condition called hemophagocytic lymphohistiocytosis (HLH). HLH can damage organs and tissues throughout the body, causing life-threatening complications. GS2 is caused by changes (mutations) in the RAB27A gene and is inherited in an autosomal recessive manner. The only current treatment that can extend survival is stem cell transplantation (a bone marrow transplant). Untreated, most children with GS2 do not survive past early childhood. Last updated: 5/1/2017

MalaCards based summary : Griscelli Syndrome, Type 2, also known as griscelli syndrome type 2, is related to griscelli syndrome, type 1 and griscelli syndrome, and has symptoms including fever, seizures and nausea and vomiting. An important gene associated with Griscelli Syndrome, Type 2 is RAB27A (RAB27A, Member RAS Oncogene Family), and among its related pathways/superpathways are Interleukin-10 signaling and wtCFTR and deltaF508 traffic / Late endosome and Lysosome (norm and CF). Affiliated tissues include skin, bone and bone marrow, and related phenotypes are immune system and hematopoietic system

Disease Ontology : 12 A Griscelli syndrome characterized by silvery gray sheen of the hair, hypopigmentation of the skin and immunodeficiency with or without neurologic impairment that has material basis in mutation in the RAB27A gene on chromosome 15q21.3.

UniProtKB/Swiss-Prot : 71 Griscelli syndrome 2: Rare autosomal recessive disorder that results in pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts, and an accumulation of melanosomes in melanocytes. GS2 patients also develop an uncontrolled T-lymphocyte and macrophage activation syndrome, known as hemophagocytic syndrome, leading to death in the absence of bone marrow transplantation. Neurological impairment is present in some patients, likely as a result of hemophagocytic syndrome.

Wikipedia : 72 Griscelli syndrome type 2 (also known as \"partial albinism with immunodeficiency\") is a rare autosomal... more...

Description from OMIM: 607624

Related Diseases for Griscelli Syndrome, Type 2

Diseases in the Griscelli Syndrome family:

Griscelli Syndrome, Type 1 Griscelli Syndrome, Type 2
Griscelli Syndrome, Type 3

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

(show all 32)
# Related Disease Score Top Affiliating Genes
1 griscelli syndrome, type 1 31.9 MYO5A RAB27A
2 griscelli syndrome 29.9 CCL5 IL10 LYST MLPH MYO5A RAB27A
3 hemophagocytic lymphohistiocytosis 28.2 IL10 LYST RAB27A UNC13B UNC13D
4 hemophagocytic lymphohistiocytosis, familial, 4 10.1 RAB27A UNC13D
5 macrophage activation syndrome 10.1 RAB27A UNC13D
6 vulvovaginitis 10.1 CCL5 IL10
7 orofacial granulomatosis 10.1 CCL5 IL10
8 radiculopathy 10.1 CCL5 IL10
9 mycetoma 10.1 CCL5 IL10
10 genital herpes 10.1 CCL5 IL10
11 spotted fever 10.1 CCL5 IL10
12 viral encephalitis 10.1 CCL5 IL10
13 polyradiculoneuropathy 10.1 CCL5 IL10
14 idiopathic neutropenia 10.1 CCL5 IL10
15 lymphatic system disease 10.1 RAB27A UNC13D
16 tropical spastic paraparesis 10.0 CCL5 IL10
17 human immunodeficiency virus infectious disease 10.0 CCL5 IL10
18 griscelli syndrome, type 3 10.0 MLPH MYO5A RAB27A
19 piebald trait 10.0 MLPH MYO5A RAB27A
20 extrinsic allergic alveolitis 10.0 CCL5 IL10
21 hematopoietic stem cell transplantation 10.0
22 filariasis 10.0 CCL5 IL10
23 bronchial disease 10.0 CCL5 IL10
24 autoinflammation, lipodystrophy, and dermatosis syndrome 10.0 CCL5 IL10
25 helicobacter pylori infection 9.9 CCL5 IL10
26 respiratory system disease 9.9 CCL5 IL10
27 myositis 9.9
28 lymphomatoid granulomatosis 9.9
29 bronchiolitis 9.9 CCL5 IL10
30 relapsing-remitting multiple sclerosis 9.8 CCL5 IL10
31 chediak-higashi syndrome 9.8 LYST RAB27A UNC13D
32 trypanosomiasis 9.6 CCL5 IL10

Graphical network of the top 20 diseases related to Griscelli Syndrome, Type 2:



Diseases related to Griscelli Syndrome, Type 2

Symptoms & Phenotypes for Griscelli Syndrome, Type 2

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
seizures
spasticity
cerebellar signs
variable neurologic deterioration (likely result of hemophagocytic syndrome)

Skin Nails Hair Skin:
skin hypopigmentation
accumulation of melanosomes in melanocytes

Skin Nails Hair Hair:
silver-gray hair
melanin pigment aggregation in hair shafts

Immunology:
hemophagocytic syndrome (hs) characterized by acute onset of uncontrolled t-lymphocyte and macrophage activation
lymphohistiocytic infiltration and hemophagocytosis in multiple organs
t-cells show reduced cytotoxicity and reduced cytolytic granule exocytosis
deficiency of delayed skin hypersensitivity
humoral deficiency (likely result of t-cell abnormalities)
more

Clinical features from OMIM:

607624

Human phenotypes related to Griscelli Syndrome, Type 2:

55 31 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 fever 55 31 occasional (7.5%) Occasional (29-5%) HP:0001945
2 seizures 55 31 occasional (7.5%) Occasional (29-5%) HP:0001250
3 nausea and vomiting 55 31 occasional (7.5%) Occasional (29-5%) HP:0002017
4 splenomegaly 55 31 hallmark (90%) Very frequent (99-80%) HP:0001744
5 hepatomegaly 55 31 hallmark (90%) Very frequent (99-80%) HP:0002240
6 hypertonia 55 31 occasional (7.5%) Occasional (29-5%) HP:0001276
7 immunodeficiency 55 31 hallmark (90%) Very frequent (99-80%) HP:0002721
8 pancytopenia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001876
9 jaundice 55 31 frequent (33%) Frequent (79-30%) HP:0000952
10 premature graying of hair 55 31 hallmark (90%) Very frequent (99-80%) HP:0002216
11 hypopigmentation of hair 55 31 hallmark (90%) Very frequent (99-80%) HP:0005599
12 hyperlipidemia 55 31 frequent (33%) Frequent (79-30%) HP:0003077
13 neutropenia 55 31 frequent (33%) Frequent (79-30%) HP:0001875
14 petechiae 55 31 occasional (7.5%) Occasional (29-5%) HP:0000967
15 lymphadenopathy 55 31 frequent (33%) Frequent (79-30%) HP:0002716
16 iris hypopigmentation 55 31 occasional (7.5%) Occasional (29-5%) HP:0007730
17 partial albinism 55 31 hallmark (90%) Very frequent (99-80%) HP:0007443
18 pulmonary infiltrates 55 31 occasional (7.5%) Occasional (29-5%) HP:0002113
19 hemophagocytosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0012156
20 spasticity 31 HP:0001257
21 abnormality of the cerebellum 31 HP:0001317
22 recurrent bacterial infections 31 HP:0002718
23 hypopigmentation of the skin 31 HP:0001010
24 silver-gray hair 31 HP:0002218
25 progressive neurologic deterioration 31 occasional (7.5%) HP:0002344
26 accumulation of melanosomes in melanocytes 31 HP:0001008
27 melanin pigment aggregation in hair shafts 31 HP:0002220
28 reduced delayed hypersensitivity 31 HP:0002972

UMLS symptoms related to Griscelli Syndrome, Type 2:


cerebellar signs, seizures, muscle spasticity

MGI Mouse Phenotypes related to Griscelli Syndrome, Type 2:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 immune system MP:0005387 9.87 CCL5 IL10 LYST MLPH MYO5A RAB27A
2 hematopoietic system MP:0005397 9.85 CCL5 IL10 LYST MYO5A RAB27A UNC13D
3 integument MP:0010771 9.65 IL10 LYST MLPH MYO5A RAB27A
4 nervous system MP:0003631 9.63 IL10 LYST MYO5A RAB27A UNC13B UNC13D
5 pigmentation MP:0001186 9.26 MLPH MYO5A RAB27A LYST
6 vision/eye MP:0005391 9.1 IL10 LYST MLPH MYO5A RAB27A UNC13B

Drugs & Therapeutics for Griscelli Syndrome, Type 2

Search Clinical Trials , NIH Clinical Center for Griscelli Syndrome, Type 2

Cochrane evidence based reviews: griscelli syndrome type 2

Genetic Tests for Griscelli Syndrome, Type 2

Genetic tests related to Griscelli Syndrome, Type 2:

# Genetic test Affiliating Genes
1 Griscelli Syndrome Type 2 28 RAB27A

Anatomical Context for Griscelli Syndrome, Type 2

MalaCards organs/tissues related to Griscelli Syndrome, Type 2:

38
Skin, Bone, Bone Marrow, T Cells, Eye, Cerebellum

Publications for Griscelli Syndrome, Type 2

Articles related to Griscelli Syndrome, Type 2:

(show all 22)
# Title Authors Year
1
Mutation analysis and prenatal diagnosis of a family with Griscelli syndrome type 2: two novel mutations in the RAB27A gene. ( 28484936 )
2017
2
A RAB27A duplication in several cases of Griscelli syndrome type 2: An explanation for cases lacking a genetic diagnosis. ( 28585352 )
2017
3
Griscelli syndrome type 2: A rare and fatal syndrome in a South Indian boy. ( 26960655 )
2016
4
Seizure as the presenting manifestation in griscelli syndrome type 2. ( 25801174 )
2015
5
An Indian boy with griscelli syndrome type 2: case report and review of literature. ( 25071262 )
2014
6
Griscelli syndrome type 2: a novel mutation in RAB27A gene with different clinical features in 2 siblings: a diagnostic conundrum. ( 24678334 )
2014
7
Late-onset hemophagocytic lymphohistiocytosis (HLH) in an adult female with Griscelli syndrome type 2 (GS2). ( 25544030 )
2014
8
Cerebellar involvement of Griscelli syndrome type 2. ( 25315806 )
2014
9
Hematopoietic stem cell transplantation with a reduced-intensity conditioning regimen in pediatric patients with Griscelli syndrome type 2. ( 23714271 )
2013
10
Pulmonary lymphomatoid granulomatosis in Griscelli syndrome type 2. ( 22111599 )
2011
11
A novel RAB27A mutation in a patient with Griscelli syndrome type 2. ( 21314004 )
2010
12
Clinical presentation of Griscelli syndrome type 2 and spectrum of RAB27A mutations. ( 19953648 )
2010
13
Functional characterization of two RAB27A missense mutations found in Griscelli syndrome type 2. ( 20370853 )
2010
14
Myositis in Griscelli syndrome type 2 treated with hematopoietic cell transplantation. ( 20034795 )
2010
15
Novel 47.5-kb deletion in RAB27A results in severe Griscelli Syndrome Type 2. ( 20591709 )
2010
16
Hematopoietic stem cell transplantation in Griscelli syndrome type 2: a single-center report on 10 patients. ( 19403888 )
2009
17
Griscelli syndrome type 2: long-term follow-up after unrelated donor bone marrow transplantation. ( 19270433 )
2009
18
Analysis of RAB27A gene in griscelli syndrome type 2: novel mutations including a deletion hotspot. ( 18350256 )
2008
19
A Griscelli syndrome type 2 murine model of hemophagocytic lymphohistiocytosis (HLH). ( 18991284 )
2008
20
Griscelli syndrome type 2: a rare and lethal disorder. ( 18403584 )
2008
21
Griscelli syndrome-type 2 in twin siblings: case report and update on RAB27A human mutations and gene structure. ( 19030707 )
2008
22
Griscelli syndrome type 2; a pediatric case with immunodeficiency. ( 17893437 )
2007

Variations for Griscelli Syndrome, Type 2

UniProtKB/Swiss-Prot genetic disease variations for Griscelli Syndrome, Type 2:

71
# Symbol AA change Variation ID SNP ID
1 RAB27A p.Trp73Gly VAR_010654 rs28938176
2 RAB27A p.Leu130Pro VAR_011334 rs104894498
3 RAB27A p.Ala152Pro VAR_011335 rs104894499

ClinVar genetic disease variations for Griscelli Syndrome, Type 2:

6 (show all 13)
# Gene Variation Type Significance SNP ID Assembly Location
1 RAB27A NM_183235.2(RAB27A): c.217T> G (p.Trp73Gly) single nucleotide variant Pathogenic rs28938176 GRCh37 Chromosome 15, 55522621: 55522621
2 RAB27A RAB27A, INV3DS, A-G, +3 single nucleotide variant Pathogenic
3 RAB27A RAB27A, 550C-T single nucleotide variant Pathogenic
4 RAB27A RAB27A, 67.5-KB DEL deletion Pathogenic
5 RAB27A NM_183235.2(RAB27A): c.389T> C (p.Leu130Pro) single nucleotide variant Pathogenic rs104894498 GRCh37 Chromosome 15, 55516165: 55516165
6 RAB27A NM_183235.2(RAB27A): c.454G> C (p.Ala152Pro) single nucleotide variant Pathogenic rs104894499 GRCh37 Chromosome 15, 55516100: 55516100
7 RAB27A RAB27A, 2-BP DEL, 51CT deletion Pathogenic
8 RAB27A RAB27A, IVS5, G-C, +1 single nucleotide variant Pathogenic
9 RAB27A NM_183235.2(RAB27A): c.352C> T (p.Gln118Ter) single nucleotide variant Pathogenic rs104894500 GRCh37 Chromosome 15, 55516202: 55516202
10 RAB27A NM_004580.4(RAB27A): c.514_518delCAAGC (p.Gln172Asnfs) deletion Likely pathogenic rs767481076 GRCh37 Chromosome 15, 55497853: 55497857
11 RAB27A NM_004580.4(RAB27A): c.550C> T (p.Arg184Ter) single nucleotide variant Pathogenic rs200956636 GRCh37 Chromosome 15, 55497821: 55497821
12 RAB27A NM_004580.4(RAB27A): c.2T> C (p.Met1Thr) single nucleotide variant Pathogenic rs141281020 GRCh37 Chromosome 15, 55527131: 55527131
13 RAB27A NC_000015.10: g.(?_55228589)_(55234954_?)del deletion Pathogenic GRCh38 Chromosome 15, 55228589: 55234954

Expression for Griscelli Syndrome, Type 2

Search GEO for disease gene expression data for Griscelli Syndrome, Type 2.

Pathways for Griscelli Syndrome, Type 2

Pathways related to Griscelli Syndrome, Type 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.85 CCL5 IL10
2 10.03 RAB27A UNC13D
3 10 MLPH RAB27A UNC13D

GO Terms for Griscelli Syndrome, Type 2

Cellular components related to Griscelli Syndrome, Type 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lysosome GO:0005764 9.43 MYO5A RAB27A UNC13D
2 photoreceptor outer segment GO:0001750 9.32 MYO5A RAB27A
3 exocytic vesicle GO:0070382 9.16 RAB27A UNC13D
4 late endosome GO:0005770 9.13 MYO5A RAB27A UNC13D
5 Weibel-Palade body GO:0033093 8.62 RAB27A UNC13D

Biological processes related to Griscelli Syndrome, Type 2 according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of exocytosis GO:0045921 9.49 RAB27A UNC13D
2 defense response to protozoan GO:0042832 9.48 IL10 LYST
3 melanocyte differentiation GO:0030318 9.46 MYO5A RAB27A
4 leukocyte chemotaxis GO:0030595 9.43 IL10 LYST
5 vesicle transport along actin filament GO:0030050 9.4 MLPH MYO5A
6 natural killer cell degranulation GO:0043320 9.37 RAB27A UNC13D
7 pigmentation GO:0043473 9.33 LYST MYO5A RAB27A
8 melanosome localization GO:0032400 9.32 MYO5A RAB27A
9 positive regulation of regulated secretory pathway GO:1903307 9.26 RAB27A UNC13D
10 melanosome transport GO:0032402 9.13 MLPH MYO5A RAB27A
11 exocytosis GO:0006887 9.02 CCL5 MYO5A RAB27A UNC13B UNC13D

Molecular functions related to Griscelli Syndrome, Type 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Rab GTPase binding GO:0017137 8.92 MLPH MYO5A UNC13B UNC13D

Sources for Griscelli Syndrome, Type 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
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47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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