SCN8
MCID: NTR054
MIFTS: 28

Neutropenia, Severe Congenital, 8, Autosomal Dominant (SCN8)

Categories: Blood diseases, Bone diseases, Cardiovascular diseases, Endocrine diseases, Genetic diseases, Immune diseases, Infectious diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Neutropenia, Severe Congenital, 8, Autosomal Dominant

MalaCards integrated aliases for Neutropenia, Severe Congenital, 8, Autosomal Dominant:

Name: Neutropenia, Severe Congenital, 8, Autosomal Dominant 57 29 6
Scn8 57 73
Neutropenia, Severe Congenital, 8, Autosomal Dominant, with or Without Pancreatic Dysfunction and/or Neurologic Abnormalities 57
Neutropenia, Severe Congenital 8, Autosomal Dominant 73
Shwachman-Diamond Syndrome-Like; Sdsl 57
Shwachman-Diamond Syndrome-Like 57
Sdsl 57

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal dominant

Miscellaneous:
onset in infancy or early childhood
de novo mutation (in some patients)
two main phenotypic categories (group a and group b)
patients in group a have normal psychomotor development
patients in group b have delayed development and/or autistic features
treatment with g-csf is partially or not effective


HPO:

31
neutropenia, severe congenital, 8, autosomal dominant:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM® 57 618752
OMIM Phenotypic Series 57 PS202700
MeSH 44 D009503

Summaries for Neutropenia, Severe Congenital, 8, Autosomal Dominant

OMIM® : 57 Autosomal dominant severe congenital neutropenia-8 (SCN8) is a pleiotropic disorder with the consistent feature of decreased neutrophils associated with recurrent bacterial infections apparent from early infancy. Other hematologic parameters are usually normal, although some patients may have mild anemia. Bone marrow examination shows hypocellularity with arrested maturation of the granulocyte lineage at the level of promyelocytes or myeloblasts. Treatment with granulocyte colony-stimulating factor (GCSF; 138970) is usually ineffective or only partially effective, whereas hematopoietic bone marrow transplantation is effective. A subset of patients have additional features, including exocrine pancreatic insufficiency, which resembles Shwachman-Diamond syndrome (see SDS1, 260400), and/or neurologic deficits, including developmental delay, impaired intellectual development, speech delay, and/or autistic features (summary by Carapito et al., 2017 and Bellanne-Chantelot et al., 2018). For discussion of genetic heterogeneity of severe congenital neutropenia, see SCN1 (202700). (618752) (Updated 05-Mar-2021)

MalaCards based summary : Neutropenia, Severe Congenital, 8, Autosomal Dominant, also known as scn8, is related to severe congenital neutropenia 8 and jackson-weiss syndrome. An important gene associated with Neutropenia, Severe Congenital, 8, Autosomal Dominant is SRP54 (Signal Recognition Particle 54). Affiliated tissues include bone marrow, neutrophil and bone, and related phenotypes are short stature and feeding difficulties in infancy

UniProtKB/Swiss-Prot : 73 Neutropenia, severe congenital 8, autosomal dominant: A form of severe congenital neutropenia, a disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.

Related Diseases for Neutropenia, Severe Congenital, 8, Autosomal Dominant

Graphical network of the top 20 diseases related to Neutropenia, Severe Congenital, 8, Autosomal Dominant:



Diseases related to Neutropenia, Severe Congenital, 8, Autosomal Dominant

Symptoms & Phenotypes for Neutropenia, Severe Congenital, 8, Autosomal Dominant

Human phenotypes related to Neutropenia, Severe Congenital, 8, Autosomal Dominant:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 short stature 31 very rare (1%) HP:0004322
2 feeding difficulties in infancy 31 very rare (1%) HP:0008872
3 elevated hepatic transaminase 31 very rare (1%) HP:0002910
4 exocrine pancreatic insufficiency 31 very rare (1%) HP:0001738
5 neutropenia 31 very rare (1%) HP:0001875
6 steatorrhea 31 very rare (1%) HP:0002570
7 autistic behavior 31 very rare (1%) HP:0000729
8 global developmental delay 31 HP:0001263

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Growth Height:
short stature

Immunology:
neutropenia
recurrent bacterial infections
hypocellular bone marrow
dysgranulopoiesis
maturational arrest of the granulocytic neutrophil line
more
Hematology:
anemia, mild (in some patients)
thrombocytopenia, transient (in some patients)

Abdomen Pancreas:
exocrine pancreatic insufficiency (in some patients)
fatty infiltration of the pancreas on imaging (in some patients)
decreased fecal elastase (in some patients)

Neurologic Central Nervous System:
developmental delay (group b)
impaired intellectual development (group b)
language delay (group b)

Head And Neck Mouth:
gingivitis
stomatitis

Growth Other:
poor overall growth

Head And Neck Face:
dysmorphic facial features (rare)

Muscle Soft Tissue:
hypotonia (group b)

Neurologic Behavioral Psychiatric Manifestations:
autism spectrum disorder (group b)

Clinical features from OMIM®:

618752 (Updated 05-Mar-2021)

Drugs & Therapeutics for Neutropenia, Severe Congenital, 8, Autosomal Dominant

Search Clinical Trials , NIH Clinical Center for Neutropenia, Severe Congenital, 8, Autosomal Dominant

Genetic Tests for Neutropenia, Severe Congenital, 8, Autosomal Dominant

Genetic tests related to Neutropenia, Severe Congenital, 8, Autosomal Dominant:

# Genetic test Affiliating Genes
1 Neutropenia, Severe Congenital, 8, Autosomal Dominant 29 SRP54

Anatomical Context for Neutropenia, Severe Congenital, 8, Autosomal Dominant

MalaCards organs/tissues related to Neutropenia, Severe Congenital, 8, Autosomal Dominant:

40
Bone Marrow, Neutrophil, Bone, Pancreas, Monocytes, Cardiac Myocytes

Publications for Neutropenia, Severe Congenital, 8, Autosomal Dominant

Articles related to Neutropenia, Severe Congenital, 8, Autosomal Dominant:

# Title Authors PMID Year
1
Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond-like syndrome. 57 6
29914977 2018
2
Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond-like features. 6 57
28972538 2017
3
Effects of seasonal acclimatization on thermal tolerance of inward currents in roach (Rutilus rutilus) cardiac myocytes. 61
28942482 2018

Variations for Neutropenia, Severe Congenital, 8, Autosomal Dominant

ClinVar genetic disease variations for Neutropenia, Severe Congenital, 8, Autosomal Dominant:

6
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SRP54 NM_003136.4(SRP54):c.677G>A (p.Gly226Glu) SNV Pathogenic 430850 rs1555354750 14:35482592-35482592 14:35013386-35013386
2 SRP54 NM_003136.4(SRP54):c.343A>G (p.Thr115Ala) SNV Pathogenic 430851 rs1555354200 14:35476576-35476576 14:35007370-35007370
3 SRP54 NM_003136.4(SRP54):c.337G>C (p.Gly113Arg) SNV Pathogenic 810688 rs1594996301 14:35476570-35476570 14:35007364-35007364
4 SRP54 NM_003136.4(SRP54):c.668C>A (p.Ala223Asp) SNV Pathogenic 810689 rs1595004126 14:35482583-35482583 14:35013377-35013377
5 SRP54 NM_003136.4(SRP54):c.821G>A (p.Gly274Asp) SNV Pathogenic 810690 rs1595004676 14:35483043-35483043 14:35013837-35013837
6 SRP54 NM_003136.4(SRP54):c.343_345ACA[2] (p.Thr117del) Microsatellite Pathogenic 430852 rs1555354198 14:35476575-35476577 14:35007369-35007371

UniProtKB/Swiss-Prot genetic disease variations for Neutropenia, Severe Congenital, 8, Autosomal Dominant:

73
# Symbol AA change Variation ID SNP ID
1 SRP54 p.Gly113Arg VAR_083566
2 SRP54 p.Thr115Ala VAR_083567
3 SRP54 p.Cys118Tyr VAR_083569
4 SRP54 p.Cys136Tyr VAR_083570
5 SRP54 p.Ala223Asp VAR_083571
6 SRP54 p.Gly226Glu VAR_083572
7 SRP54 p.Gly274Asp VAR_083573

Expression for Neutropenia, Severe Congenital, 8, Autosomal Dominant

Search GEO for disease gene expression data for Neutropenia, Severe Congenital, 8, Autosomal Dominant.

Pathways for Neutropenia, Severe Congenital, 8, Autosomal Dominant

GO Terms for Neutropenia, Severe Congenital, 8, Autosomal Dominant

Sources for Neutropenia, Severe Congenital, 8, Autosomal Dominant

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
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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-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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