GS1
MCID: GRS013
MIFTS: 44

Griscelli Syndrome, Type 1 (GS1)

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

Aliases & Classifications for Griscelli Syndrome, Type 1

MalaCards integrated aliases for Griscelli Syndrome, Type 1:

Name: Griscelli Syndrome, Type 1 57 13 54 39 70
Griscelli Syndrome Type 1 12 20 58 29 6 44 15
Gs1 57 12 20 72
Partial Albinism and Primary Neurologic Disease Without Hemophagocytic Syndrome 57 20
Griscelli Syndrome, Cutaneous and Neurologic Type 57 20
Hypopigmentation-Neurologic Impairment Syndrome 12 58
Griscelli Syndrome with Neurologic Impairment 57 20
Griscelli-Prunieras Syndrome Type 1 12 58
Pigmentary Dilution of the Skin and Hair, the Presence of Large Clumps of Pigment in Hair Shafts 20
Griscelli Syndrome with Primary Neurologic Impairment 72
Griscelli Syndrome, Cutaneous and Neurological Type 12
Griscelli Syndrome with Neurological Impairment 12
Griscelli Syndrome 1 72

Characteristics:

Orphanet epidemiological data:

58
griscelli syndrome type 1
Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy or early childhood
may be same entity as elejalde syndrome
see also griscelli syndrome type 2 for a similar disorder with characteristic immunologic abnormalities and
griscelli syndrome type 3 for a similar disorder without neurologic or immunologic abnormalities


HPO:

31
griscelli syndrome, type 1:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Rare skin diseases


External Ids:

Disease Ontology 12 DOID:0060832
OMIM® 57 214450
OMIM Phenotypic Series 57 PS214450
MeSH 44 C537301
MESH via Orphanet 45 C537301
ICD10 via Orphanet 33 E70.3
UMLS via Orphanet 71 C1859194
Orphanet 58 ORPHA79476
MedGen 41 C1859194
UMLS 70 C1859194

Summaries for Griscelli Syndrome, Type 1

OMIM® : 57 Griscelli syndrome type 1 (GS1) represents hypomelanosis with a primary neurologic deficit and without immunologic impairment or manifestations of hemophagocytic syndrome (Menasche et al., 2002). Griscelli syndrome with immune impairment, or Griscelli syndrome type 2 (607624), is caused by mutation in the RAB27A gene (603868). Griscelli syndrome type 3 (609227), characterized by hypomelanosis with no immunologic or neurologic manifestations, can be caused by mutation in the melanophilin (MLPH; 606526) or MYO5A genes. Griscelli syndrome is a 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. While most patients also develop hemophagocytic syndrome, leading to death in the absence of bone marrow transplantation (Menasche et al., 2000), some show severe neurologic impairment early in life without apparent immune abnormalities. Bahadoran et al. (2003) characterized GS1 as comprising hypomelanosis and severe central nervous system dysfunction, corresponding to the 'dilute' phenotype in the mouse, and GS2 as comprising hypomelanosis and lymphohistiocytotic hemophagocytosis, corresponding to the 'ashen' phenotype in mouse. Anikster et al. (2002), Menasche et al. (2002), Huizing et al. (2002), and 3,2:Bahadoran et al. (2003, 2003) suggested that Elejalde syndrome (256710) in some patients and GS1 represent the same entity. (214450) (Updated 05-Apr-2021)

MalaCards based summary : Griscelli Syndrome, Type 1, also known as griscelli syndrome type 1, is related to griscelli syndrome, type 2 and griscelli syndrome, and has symptoms including seizures An important gene associated with Griscelli Syndrome, Type 1 is MYO5A (Myosin VA), and among its related pathways/superpathways is Deregulation of Rab and Rab Effector Genes in Bladder Cancer. Affiliated tissues include eye, bone marrow and skin, and related phenotypes are nystagmus and diplopia

Disease Ontology : 12 A Griscelli syndrome characterized by silvery gray sheen of the hair, hypopigmentation of the skin and neurological impairment without immunodeficiency that has material basis in mutations in the MYO5A gene on chromosome 15q21.2.

UniProtKB/Swiss-Prot : 72 Griscelli syndrome 1: Rare autosomal recessive disorder that results in pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts, silvery-gray hair and accumulation of melanosomes in melanocytes. GS1 patients show developmental delay, hypotonia and mental retardation, without apparent immune abnormalities.

Related Diseases for Griscelli Syndrome, Type 1

Graphical network of the top 20 diseases related to Griscelli Syndrome, Type 1:



Diseases related to Griscelli Syndrome, Type 1

Symptoms & Phenotypes for Griscelli Syndrome, Type 1

Human phenotypes related to Griscelli Syndrome, Type 1:

58 31 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000639
2 diplopia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000651
3 ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001251
4 hypertonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001276
5 retinopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0000488
6 abnormality of movement 58 31 hallmark (90%) Very frequent (99-80%) HP:0100022
7 premature graying of hair 58 31 hallmark (90%) Very frequent (99-80%) HP:0002216
8 white hair 58 31 hallmark (90%) Very frequent (99-80%) HP:0011364
9 partial albinism 58 31 hallmark (90%) Very frequent (99-80%) HP:0007443
10 iris hypopigmentation 58 31 hallmark (90%) Very frequent (99-80%) HP:0007730
11 generalized hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001290
12 seizure 31 hallmark (90%) HP:0001250
13 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
14 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
15 hyperlipidemia 58 31 frequent (33%) Frequent (79-30%) HP:0003077
16 cerebral calcification 58 31 occasional (7.5%) Occasional (29-5%) HP:0002514
17 seizures 58 Very frequent (99-80%)
18 hypopigmentation of the skin 31 HP:0001010
19 silver-gray hair 31 HP:0002218
20 hypotonia 31 HP:0001252
21 accumulation of melanosomes in melanocytes 31 HP:0001008
22 melanin pigment aggregation in hair shafts 31 HP:0002220

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
hypotonia
developmental delay
mental retardation

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

Immunology:
no immunologic abnormalities

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

Head And Neck Eyes:
roving eye movements
poor visual fixation

Clinical features from OMIM®:

214450 (Updated 05-Apr-2021)

UMLS symptoms related to Griscelli Syndrome, Type 1:


seizures

MGI Mouse Phenotypes related to Griscelli Syndrome, Type 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.07 BLOC1S3 BLOC1S6 GLUL HPS4 HPS5 HPS6
2 integument MP:0010771 9.65 BLOC1S3 BLOC1S6 HPS4 HPS5 HPS6 MLPH
3 hearing/vestibular/ear MP:0005377 9.63 BLOC1S3 BLOC1S6 HPS4 HPS5 HPS6 MYO5A
4 pigmentation MP:0001186 9.23 BLOC1S3 BLOC1S6 HPS4 HPS5 HPS6 MLPH

Drugs & Therapeutics for Griscelli Syndrome, Type 1

Search Clinical Trials , NIH Clinical Center for Griscelli Syndrome, Type 1

Cochrane evidence based reviews: griscelli syndrome type 1

Genetic Tests for Griscelli Syndrome, Type 1

Genetic tests related to Griscelli Syndrome, Type 1:

# Genetic test Affiliating Genes
1 Griscelli Syndrome Type 1 29 MYO5A

Anatomical Context for Griscelli Syndrome, Type 1

MalaCards organs/tissues related to Griscelli Syndrome, Type 1:

40
Eye, Bone Marrow, Skin

Publications for Griscelli Syndrome, Type 1

Articles related to Griscelli Syndrome, Type 1:

(show all 18)
# Title Authors PMID Year
1
Evidence that Griscelli syndrome with neurological involvement is caused by mutations in RAB27A, not MYO5A. 6 57
12058346 2002
2
Two genes are responsible for Griscelli syndrome at the same 15q21 locus. 6 57
10704277 2000
3
Griscelli disease maps to chromosome 15q21 and is associated with mutations in the myosin-Va gene. 6 57
9207796 1997
4
Griscelli syndrome type 1: a report of two cases and review of the literature. 57 61
19318926 2009
5
Comment on Elejalde syndrome and relationship with Griscelli syndrome. 57
12522801 2003
6
Hypomelanosis, immunity, central nervous system: no more "and", not the end. 57
12522786 2003
7
Griscelli syndrome types 1 and 2. 57
12452176 2002
8
The role of cytotoxicity in lymphocyte homeostasis. 57
11544002 2001
9
12-year-old male with Elejalde syndrome (neuroectodermal melanolysosomal disease). 57
11170073 2001
10
Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome. 57
10835631 2000
11
Elejalde syndrome--a melanolysosomal neurocutaneous syndrome: clinical and morphological findings in 7 patients. 57
10052404 1999
12
A syndrome associating partial albinism and immunodeficiency. 57
707528 1978
13
Myosin Va mutation in rats is an animal model for the human hereditary neurological disease, Griscelli syndrome type 1. 54 61
17185506 2006
14
Myosin Va is required for normal photoreceptor synaptic activity. 61 54
15316067 2004
15
Genetic analysis in three Egyptian patients with Griscelli syndrome Type 1 reveals new nonsense mutations in MYO5A. 61
32275080 2020
16
Myosin Va and spermine synthase: partners in exosome transport. 61
30967493 2019
17
Absence of platelet phenotype in mice lacking the motor protein myosin Va. 61
23349704 2013
18
A role for myosin Va in cerebellar plasticity and motor learning: a possible mechanism underlying neurological disorder in myosin Va disease. 61
21508232 2011

Variations for Griscelli Syndrome, Type 1

ClinVar genetic disease variations for Griscelli Syndrome, Type 1:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MYO5A NM_000259.3(MYO5A):c.2332C>T (p.Arg778Ter) SNV Pathogenic 14069 rs764371254 GRCh37: 15:52668632-52668632
GRCh38: 15:52376435-52376435
2 MYO5A MYO5A, 47-BP INS, NT4634 Insertion Pathogenic 14070 GRCh37:
GRCh38:
3 MYO5A NM_000259.3(MYO5A):c.2012+1G>T SNV Pathogenic 561060 rs769021352 GRCh37: 15:52675287-52675287
GRCh38: 15:52383090-52383090
4 MYO5A NM_001382347.1(MYO5A):c.3604G>T (p.Glu1202Ter) SNV Pathogenic 998280 GRCh37: 15:52645819-52645819
GRCh38: 15:52353622-52353622
5 MYO5A NM_000259.3(MYO5A):c.2477G>A (p.Arg826His) SNV Uncertain significance 742942 rs752461164 GRCh37: 15:52667601-52667601
GRCh38: 15:52375404-52375404
6 MYO5A NM_000259.3(MYO5A):c.3098T>G (p.Leu1033Trp) SNV Uncertain significance 592085 rs751411629 GRCh37: 15:52659290-52659290
GRCh38: 15:52367093-52367093
7 MYO5A NM_000259.3(MYO5A):c.1543-84del Deletion Benign 803099 rs71425744 GRCh37: 15:52681644-52681644
GRCh38: 15:52389447-52389447
8 MYO5A NM_000259.3(MYO5A):c.3736C>T (p.Arg1246Cys) SNV Benign 255650 rs1058219 GRCh37: 15:52643564-52643564
GRCh38: 15:52351367-52351367

Expression for Griscelli Syndrome, Type 1

Search GEO for disease gene expression data for Griscelli Syndrome, Type 1.

Pathways for Griscelli Syndrome, Type 1

Pathways related to Griscelli Syndrome, Type 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.23 SYTL3 SYTL2 RAB27A MYRIP MLPH

GO Terms for Griscelli Syndrome, Type 1

Cellular components related to Griscelli Syndrome, Type 1 according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 10.25 SYTL2 RILPL2 RAB15 MYRIP MYO5C MYO5B
2 extracellular exosome GO:0070062 10.08 RAB27A RAB15 MYO5C MYO5B MYO5A MLPH
3 endosome GO:0005768 9.92 RAB27A RAB15 RAB11FIP2 HPS6 BLOC1S6
4 recycling endosome GO:0055037 9.69 RAB15 MYO5B MYO5A
5 actin cytoskeleton GO:0015629 9.67 MYRIP MYO5C MYO5B MYO5A
6 transport vesicle GO:0030133 9.61 MYRIP BLOC1S6 BLOC1S3
7 extrinsic component of plasma membrane GO:0019897 9.49 SYTL3 SYTL2
8 BLOC-1 complex GO:0031083 9.46 BLOC1S6 BLOC1S3
9 myosin complex GO:0016459 9.43 MYO5C MYO5B MYO5A
10 insulin-responsive compartment GO:0032593 9.32 RAB15 MYO5A
11 BLOC-2 complex GO:0031084 9.16 HPS6 HPS5
12 exocytic vesicle GO:0070382 9.13 SYTL3 SYTL2 RAB27A
13 melanosome GO:0042470 9.02 SYTL2 RAB27A MYRIP MYO5A HPS4

Biological processes related to Griscelli Syndrome, Type 1 according to GeneCards Suite gene sharing:

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 protein transport GO:0015031 9.95 RILPL2 RAB15 RAB11FIP2 MYO5B MYO5A
2 intracellular protein transport GO:0006886 9.83 SYTL3 SYTL2 MYRIP MLPH
3 vesicle-mediated transport GO:0016192 9.8 SYTL2 RAB27A MYO5B MYO5A HPS4
4 actin filament organization GO:0007015 9.74 MYO5C MYO5B MYO5A
5 blood coagulation GO:0007596 9.73 RAB27A HPS6 HPS5 HPS4 BLOC1S6 BLOC1S3
6 exocytosis GO:0006887 9.71 SYTL3 SYTL2 RAB27A
7 anterograde axonal transport GO:0008089 9.58 BLOC1S6 BLOC1S3
8 melanosome organization GO:0032438 9.56 BLOC1S6 BLOC1S3
9 vesicle transport along actin filament GO:0030050 9.54 MYO5C MYO5B MYO5A
10 anterograde synaptic vesicle transport GO:0048490 9.51 BLOC1S6 BLOC1S3
11 organelle organization GO:0006996 9.5 HPS6 HPS5 HPS4
12 endosome to melanosome transport GO:0035646 9.49 BLOC1S6 BLOC1S3
13 positive regulation of natural killer cell activation GO:0032816 9.48 BLOC1S6 BLOC1S3
14 positive regulation of regulated secretory pathway GO:1903307 9.46 RAB27A RAB15
15 melanocyte differentiation GO:0030318 9.46 RAB27A HPS6 HPS4 BLOC1S6
16 secretion of lysosomal enzymes GO:0033299 9.43 BLOC1S6 BLOC1S3
17 pigmentation GO:0043473 9.35 RAB27A HPS6 HPS5 BLOC1S6 BLOC1S3
18 melanosome transport GO:0032402 9.02 RAB27A MYO5A MLPH BLOC1S6 BLOC1S3

Molecular functions related to Griscelli Syndrome, Type 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.38 SYTL3 SYTL2 SERINC1 RILPL2 RAB27A RAB15
2 actin binding GO:0003779 9.72 MYRIP MYO5C MYO5B MYO5A MLPH
3 actin filament binding GO:0051015 9.67 MYO5C MYO5B MYO5A BLOC1S6
4 motor activity GO:0003774 9.63 MYO5C MYO5B MYO5A
5 small GTPase binding GO:0031267 9.5 RAB11FIP2 MYRIP MYO5B MYO5A MLPH HPS6
6 myosin binding GO:0017022 9.48 MYRIP MLPH
7 neurexin family protein binding GO:0042043 9.43 SYTL3 SYTL2
8 microfilament motor activity GO:0000146 9.43 MYO5C MYO5B MYO5A
9 actin-dependent ATPase activity GO:0030898 9.33 MYO5C MYO5B MYO5A
10 Rab GTPase binding GO:0017137 9.02 SYTL3 SYTL2 RAB11FIP2 MYRIP MLPH

Sources for Griscelli Syndrome, Type 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....