MCID: GRS014
MIFTS: 53

Griscelli Syndrome, Type 2

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

Aliases & Classifications for Griscelli Syndrome, Type 2

MalaCards integrated aliases for Griscelli Syndrome, Type 2:

Name: Griscelli Syndrome, Type 2 54 24 13 52 69
Griscelli Syndrome Type 2 12 50 29 42 14
Hypopigmentation-Immunodeficiency with or Without Neurologic Impairment Syndrome 12 50 56
Griscelli-Pruniéras Syndrome Type 2 12 50 56
Gs2 12 50 71
Griscelli Syndrome with Hemophagocytic Syndrome 12 50
Partial Albinism and Immunodeficiency Syndrome 12 50
Paid Syndrome 12 50
Griscelli Disease Type 2 56
Griscelli Syndrome 2 71
Paid Sndrome 24

Characteristics:

Orphanet epidemiological data:

56
griscelli disease type 2
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy; Age of death: late childhood;

OMIM:

54
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:

32
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 : 50 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 and griscelli syndrome, type 1, and has symptoms including neutropenia, hepatomegaly and splenomegaly. 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). The drugs alemtuzumab and Busulfan have been mentioned in the context of this disorder. 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.

Description from OMIM: 607624

Related Diseases for Griscelli Syndrome, Type 2

Diseases in the Griscelli Syndrome family:

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

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

(show all 34)
id Related Disease Score Top Affiliating Genes
1 griscelli syndrome 11.4
2 griscelli syndrome, type 1 10.9
3 macular dystrophy, atypical vitelliform 10.2 RAB27A UNC13D
4 hidradenitis suppurativa 10.2 CCL5 IL10
5 oropharyngeal cancer, childhood 10.2 CCL5 IL10
6 vascular dementia 10.2 CCL5 IL10
7 myofascial pain syndrome 10.2 CCL5 IL10
8 mycobacterium gordonae 10.2 CCL5 IL10
9 psychologic dyspareunia 10.2 CCL5 IL10
10 dysphagia 10.2 CCL5 IL10
11 epidermolysis bullosa acquisita 10.2 CCL5 IL10
12 ovarian mucinous adenofibroma 10.2 CCL5 IL10
13 iida kannari syndrome 10.2 CCL5 IL10
14 pediatric supratentorial ependymoma 10.1 RAB27A UNC13D
15 myelitis 10.1 CCL5 IL10
16 heart sarcoma 10.1 CCL5 IL10
17 crigler-najjar syndrome, type i 10.1 MLPH MYO5A RAB27A
18 periventricular nodular heterotopia 3 10.1 MLPH MYO5A RAB27A
19 carcinoma arising in nasal papillomatosis 10.1 CCL5 IL10
20 gastric ulcer 10.1 CCL5 IL10
21 spontaneous ocular nystagmus 10.0 CCL5 IL10
22 ragweed sensitivity 10.0 CCL5 IL10
23 hematopoietic stem cell transplantation 10.0
24 hemophagocytic lymphohistiocytosis 10.0
25 acute chest syndrome 9.9 CCL5 IL10
26 inner ear disease 9.9 CCL5 IL10
27 lymphomatoid granulomatosis 9.8
28 myositis 9.8
29 hyperpigmentation of eyelid 9.8 CCL5 IL10
30 chediak-higashi syndrome 9.7 LYST RAB27A UNC13D
31 neonatal jaundice 9.6 CCL5 IL10
32 hepatitis b 8.4 IL10 LYST RAB27A UNC13B UNC13D
33 salmonellosis 8.0 CCL5 IL10 LYST MLPH MYO5A RAB27A
34 craniosynostosis 3 7.1 CCL5 IL10 LYST MLPH MYO5A RAB27A

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:

54

Neurologic- Central Nervous System:
spasticity
seizures
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:

56 32 (show all 28)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 neutropenia 56 32 frequent (33%) Frequent (79-30%) HP:0001875
2 hepatomegaly 56 32 hallmark (90%) Very frequent (99-80%) HP:0002240
3 splenomegaly 56 32 hallmark (90%) Very frequent (99-80%) HP:0001744
4 jaundice 56 32 frequent (33%) Frequent (79-30%) HP:0000952
5 seizures 56 32 occasional (7.5%) Occasional (29-5%) HP:0001250
6 hypertonia 56 32 occasional (7.5%) Occasional (29-5%) HP:0001276
7 hyperlipidemia 56 32 frequent (33%) Frequent (79-30%) HP:0003077
8 immunodeficiency 56 32 hallmark (90%) Very frequent (99-80%) HP:0002721
9 pancytopenia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001876
10 petechiae 56 32 occasional (7.5%) Occasional (29-5%) HP:0000967
11 fever 56 32 occasional (7.5%) Occasional (29-5%) HP:0001945
12 lymphadenopathy 56 32 frequent (33%) Frequent (79-30%) HP:0002716
13 premature graying of hair 56 32 hallmark (90%) Very frequent (99-80%) HP:0002216
14 pulmonary infiltrates 56 32 occasional (7.5%) Occasional (29-5%) HP:0002113
15 nausea and vomiting 56 32 occasional (7.5%) Occasional (29-5%) HP:0002017
16 hypopigmentation of hair 56 32 hallmark (90%) Very frequent (99-80%) HP:0005599
17 iris hypopigmentation 56 32 occasional (7.5%) Occasional (29-5%) HP:0007730
18 partial albinism 56 32 hallmark (90%) Very frequent (99-80%) HP:0007443
19 hemophagocytosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0012156
20 spasticity 32 HP:0001257
21 progressive neurologic deterioration 32 occasional (7.5%) HP:0002344
22 recurrent bacterial infections 32 HP:0002718
23 silver-gray hair 32 HP:0002218
24 reduced delayed hypersensitivity 32 HP:0002972
25 accumulation of melanosomes in melanocytes 32 HP:0001008
26 melanin pigment aggregation in hair shafts 32 HP:0002220
27 abnormality of the cerebellum 32 HP:0001317
28 hypopigmentation of the skin 32 HP:0001010

UMLS symptoms related to Griscelli Syndrome, Type 2:


muscle spasticity, seizures

MGI Mouse Phenotypes related to Griscelli Syndrome, Type 2:

44
id 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 MLPH MYO5A RAB27A IL10 LYST
4 nervous system MP:0003631 9.63 IL10 LYST MYO5A RAB27A UNC13B UNC13D
5 pigmentation MP:0001186 9.26 LYST MLPH MYO5A RAB27A
6 vision/eye MP:0005391 9.1 IL10 LYST MLPH MYO5A RAB27A UNC13B

Drugs & Therapeutics for Griscelli Syndrome, Type 2

Drugs for Griscelli Syndrome, Type 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 15)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
alemtuzumab Approved, Investigational 216503-57-0
2
Busulfan Approved, Investigational 55-98-1 2478
3
Cyclophosphamide Approved, Investigational 50-18-0, 6055-19-2 2907
4
Fludarabine Approved 21679-14-1, 75607-67-9 30751
5
Melphalan Approved 148-82-3 4053 460612
6
Mesna Approved 3375-50-6 598
7
Vidarabine Approved 24356-66-9 32326 21704
8 Alkylating Agents
9 Anti-Infective Agents
10 Antimetabolites
11 Antimetabolites, Antineoplastic
12 Antirheumatic Agents
13 Antiviral Agents
14 Immunosuppressive Agents
15 Protective Agents

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies Recruiting NCT01652092 Alemtuzumab 0.3 mg;Cyclophosphamide;Busulfan;Fludarabine phosphate 40 mg;Melphalan;Alemtuzumab 0.2 mg;Busulfan;Fludarabine phosphate 30 mg;MESNA

Search 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:

id Genetic test Affiliating Genes
1 Griscelli Syndrome Type 2 29
2 Griscelli Syndrome, Type 2 24 RAB27A

Anatomical Context for Griscelli Syndrome, Type 2

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

39
Skin, Bone, Bone Marrow, T Cells, Eye, Cerebellum

Publications for Griscelli Syndrome, Type 2

Articles related to Griscelli Syndrome, Type 2:

(show all 22)
id 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
Griscelli syndrome type 2: a novel mutation in RAB27A gene with different clinical features in 2 siblings: a diagnostic conundrum. ( 24678334 )
2014
6
Cerebellar involvement of Griscelli syndrome type 2. ( 25315806 )
2014
7
Late-onset hemophagocytic lymphohistiocytosis (HLH) in an adult female with Griscelli syndrome type 2 (GS2). ( 25544030 )
2014
8
An Indian boy with griscelli syndrome type 2: case report and review of literature. ( 25071262 )
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
Myositis in Griscelli syndrome type 2 treated with hematopoietic cell transplantation. ( 20034795 )
2010
13
Functional characterization of two RAB27A missense mutations found in Griscelli syndrome type 2. ( 20370853 )
2010
14
Novel 47.5-kb deletion in RAB27A results in severe Griscelli Syndrome Type 2. ( 20591709 )
2010
15
Clinical presentation of Griscelli syndrome type 2 and spectrum of RAB27A mutations. ( 19953648 )
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
A Griscelli syndrome type 2 murine model of hemophagocytic lymphohistiocytosis (HLH). ( 18991284 )
2008
19
Griscelli syndrome-type 2 in twin siblings: case report and update on RAB27A human mutations and gene structure. ( 19030707 )
2008
20
Griscelli syndrome type 2: a rare and lethal disorder. ( 18403584 )
2008
21
Analysis of RAB27A gene in griscelli syndrome type 2: novel mutations including a deletion hotspot. ( 18350256 )
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
id 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 12)
id 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

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:

id 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:

id 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)
id 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 melanosome transport GO:0032402 9.46 MYO5A RAB27A
4 melanocyte differentiation GO:0030318 9.43 MYO5A RAB27A
5 leukocyte chemotaxis GO:0030595 9.4 IL10 LYST
6 natural killer cell degranulation GO:0043320 9.32 RAB27A UNC13D
7 melanosome localization GO:0032400 9.26 MYO5A RAB27A
8 positive regulation of regulated secretory pathway GO:1903307 9.16 RAB27A UNC13D
9 pigmentation GO:0043473 9.13 LYST MYO5A RAB27A
10 vesicle transport along actin filament GO:0030050 9.07 MYO5A
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:

id 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
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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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