HBSL
MCID: HYP530
MIFTS: 31

Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity (HBSL)

Categories: Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Hypomyelination with Brainstem and Spinal Cord Involvement and...

MalaCards integrated aliases for Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity:

Name: Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity 57 43 72 36 29 6 70
Hbsl 57 43 58 72
Hypomyelination with Brain Stem and Spinal Cord Involvement and Leg Spasticity 43 58
Aspartyl-Trna Synthetase Deficiency 57 43

Characteristics:

Orphanet epidemiological data:

58
hypomyelination with brain stem and spinal cord involvement and leg spasticity
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

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

Miscellaneous:
progressive disorder
onset in first year of life


HPO:

31
hypomyelination with brainstem and spinal cord involvement and leg spasticity:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset progressive


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

OMIM® 57 615281
KEGG 36 H02433
ICD10 via Orphanet 33 E75.2
Orphanet 58 ORPHA363412
UMLS 70 C3809008

Summaries for Hypomyelination with Brainstem and Spinal Cord Involvement and...

MedlinePlus Genetics : 43 Hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL) is a condition that affects the brain and spinal cord (central nervous system). In particular, the condition affects nerves in specific regions (called tracts) within the spinal cord and the brainstem, which is the part of the brain that connects to the spinal cord. HBSL is a form of leukodystrophy, which is a group of conditions that involve abnormalities of the nervous system's white matter. The white matter consists of nerve fibers covered by a fatty substance, called myelin, that insulates the fibers and promotes the rapid transmission of nerve impulses. In HBSL, the nervous system has a reduced ability to form myelin (hypomyelination).In HBSL, early development of motor skills (such as rolling over and sitting) may be normal, but movement problems typically begin within the infant's first year. However, in some individuals, these problems do not appear until adolescence. The characteristic feature of HBSL is muscle stiffness (spasticity) in the legs that worsens over time. Most people with HBSL are unable to walk independently. Other neurological problems in affected individuals can include abnormal side-to-side movements of the eyes (nystagmus), weak muscle tone (hypotonia) in the torso, and mild intellectual disability.Distinct changes in the brains of people with HBSL can be seen using magnetic resonance imaging (MRI). These characteristic abnormalities typically involve specific regions (called tracts) within the brainstem and spinal cord, especially the pyramidal tract, lateral corticospinal tract, and the dorsal column.

MalaCards based summary : Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity, also known as hbsl, is related to leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation and autosomal recessive disease. An important gene associated with Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity is DARS1 (Aspartyl-TRNA Synthetase 1), and among its related pathways/superpathways is Aminoacyl-tRNA biosynthesis. Affiliated tissues include spinal cord, cerebellum and brain, and related phenotypes are intellectual disability, mild and spasticity

OMIM® : 57 Hypomyelination with brainstem and spinal cord involvement and leg spasticity is an autosomal recessive leukoencephalopathy characterized by onset in the first year of life of severe spasticity, mainly affecting the lower limbs and resulting in an inability to achieve independent ambulation. Affected individuals show delayed motor development and nystagmus; some may have mild mental retardation. Brain MRI shows hypomyelination and white matter lesions in the cerebrum, brainstem, cerebellum, and spinal cord (summary by Taft et al., 2013). (615281) (Updated 05-Apr-2021)

KEGG : 36 Hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL) is characterized by focal cerebral white matter abnormalities and spinal cord signal abnormalities. HBSL is the result of mutations in DARS, a cytoplasmic tRNA synthetase gene.

UniProtKB/Swiss-Prot : 72 Hypomyelination with brainstem and spinal cord involvement and leg spasticity: An autosomal recessive leukoencephalopathy characterized by onset in the first year of life of severe spasticity, mainly affecting the lower limbs and resulting in an inability to achieve independent ambulation. Affected individuals show delayed motor development and nystagmus; some may have mild mental retardation. Brain MRI shows hypomyelination and white matter lesions in the cerebrum, brainstem, cerebellum, and spinal cord.

Related Diseases for Hypomyelination with Brainstem and Spinal Cord Involvement and...

Diseases related to Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation 11.8
2 autosomal recessive disease 10.2
3 leukodystrophy 10.1
4 spasticity 10.1
5 ataxia and polyneuropathy, adult-onset 9.9
6 microphthalmia 9.9
7 hydrocephalus 9.9
8 peripheral nervous system disease 9.9
9 neuropathy 9.9
10 pathologic nystagmus 9.9

Graphical network of the top 20 diseases related to Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity:



Diseases related to Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity

Symptoms & Phenotypes for Hypomyelination with Brainstem and Spinal Cord Involvement and...

Human phenotypes related to Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity:

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 intellectual disability, mild 31 occasional (7.5%) HP:0001256
2 spasticity 31 HP:0001257
3 hyperreflexia 31 HP:0001347
4 nystagmus 31 HP:0000639
5 motor delay 31 HP:0001270
6 babinski sign 31 HP:0003487
7 hypoplasia of the corpus callosum 31 HP:0002079
8 leukoencephalopathy 31 HP:0002352
9 muscular hypotonia of the trunk 31 HP:0008936
10 cns hypomyelination 31 HP:0003429

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
hyperreflexia
leukoencephalopathy
delayed motor development
mental retardation, mild (in some patients)
hypomyelination
more
Head And Neck Eyes:
nystagmus
pallor of the optic disks (in some patients)

Clinical features from OMIM®:

615281 (Updated 05-Apr-2021)

Drugs & Therapeutics for Hypomyelination with Brainstem and Spinal Cord Involvement and...

Search Clinical Trials , NIH Clinical Center for Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity

Genetic Tests for Hypomyelination with Brainstem and Spinal Cord Involvement and...

Genetic tests related to Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity:

# Genetic test Affiliating Genes
1 Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity 29 DARS1

Anatomical Context for Hypomyelination with Brainstem and Spinal Cord Involvement and...

MalaCards organs/tissues related to Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity:

40
Spinal Cord, Cerebellum, Brain

Publications for Hypomyelination with Brainstem and Spinal Cord Involvement and...

Articles related to Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity:

(show all 13)
# Title Authors PMID Year
1
Mutations in DARS cause hypomyelination with brain stem and spinal cord involvement and leg spasticity. 57 6 61
23643384 2013
2
Lithium in groundwater used for drinking-water supply in the United States. 61
33454610 2021
3
Simulation design and students' satisfaction with home-based simulation learning in oral health therapy. 61
33660871 2021
4
The relation of geogenic contaminants to groundwater age, aquifer hydrologic position, water type, and redox conditions in Atlantic and Gulf Coastal Plain aquifers, eastern and south-central USA. 61
32392689 2020
5
The Leukodystrophies HBSL and LBSL-Correlates and Distinctions. 61
33574740 2020
6
An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies. 61
31829048 2020
7
A Hypomorphic Dars1D367Y Model Recapitulates Key Aspects of the Leukodystrophy HBSL. 61
33551752 2020
8
[DARS mutations responsible for hypomyelination with brain stem and spinal cord involvement and leg spasticity: report of two cases and review of literature]. 61
29518832 2018
9
Expression Pattern of the Aspartyl-tRNA Synthetase DARS in the Human Brain. 61
29615866 2018
10
In vivocharacterization of the aspartyl-tRNA synthetase DARS: Homing in on the leukodystrophy HBSL. 61
27816769 2017
11
DARS-associated leukoencephalopathy can mimic a steroid-responsive neuroinflammatory disorder. 61
25527264 2015
12
Removing N-terminal sequences in pre-S1 domain enhanced antibody and B-cell responses by an HBV large surface antigen DNA vaccine. 61
22844502 2012
13
Leadership development for program directors. 61
22132267 2010

Variations for Hypomyelination with Brainstem and Spinal Cord Involvement and...

ClinVar genetic disease variations for Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity:

6 (show all 15)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 DARS1 NM_001349.4(DARS1):c.1099G>T (p.Asp367Tyr) SNV Pathogenic 50986 rs370064817 GRCh37: 2:136673803-136673803
GRCh38: 2:135916233-135916233
2 DARS1 NM_001349.4(DARS1):c.821C>T (p.Ala274Val) SNV Pathogenic 50987 rs369152939 GRCh37: 2:136678161-136678161
GRCh38: 2:135920591-135920591
3 DARS1 NM_001349.4(DARS1):c.766A>C (p.Met256Leu) SNV Pathogenic 50988 rs886037635 GRCh37: 2:136680399-136680399
GRCh38: 2:135922829-135922829
4 DARS1 NM_001349.4(DARS1):c.1379G>A (p.Arg460His) SNV Pathogenic 50990 rs587776985 GRCh37: 2:136668744-136668744
GRCh38: 2:135911174-135911174
5 DARS1 NM_001349.4(DARS1):c.1480C>G (p.Arg494Gly) SNV Pathogenic 50991 rs147077598 GRCh37: 2:136664912-136664912
GRCh38: 2:135907342-135907342
6 DARS1 NM_001349.4(DARS1):c.839A>T (p.His280Leu) SNV Pathogenic 143190 rs527236040 GRCh37: 2:136678143-136678143
GRCh38: 2:135920573-135920573
7 DARS1 NM_001349.4(DARS1):c.1459C>T (p.Arg487Cys) SNV Pathogenic 50989 rs587776984 GRCh37: 2:136664933-136664933
GRCh38: 2:135907363-135907363
8 DARS1 NM_001349.4(DARS1):c.1481G>A (p.Arg494His) SNV Likely pathogenic 522693 rs967111310 GRCh37: 2:136664911-136664911
GRCh38: 2:135907341-135907341
9 DARS1 NM_001349.4(DARS1):c.1277T>C (p.Leu426Ser) SNV Likely pathogenic 488394 rs377510027 GRCh37: 2:136669017-136669017
GRCh38: 2:135911447-135911447
10 DARS1 NM_001349.4(DARS1):c.242G>A (p.Arg81His) SNV Uncertain significance 488395 rs532864330 GRCh37: 2:136719044-136719044
GRCh38: 2:135961474-135961474
11 DARS1 NM_001349.4(DARS1):c.845A>C (p.His282Pro) SNV Uncertain significance 982592 GRCh37: 2:136678137-136678137
GRCh38: 2:135920567-135920567
12 DARS1 NM_001349.4(DARS1):c.644T>C (p.Phe215Ser) SNV Uncertain significance 1030430 GRCh37: 2:136681989-136681989
GRCh38: 2:135924419-135924419
13 DARS1 NM_001349.4(DARS1):c.125-18C>T SNV Uncertain significance 512090 rs777497235 GRCh37: 2:136736954-136736954
GRCh38: 2:135979384-135979384
14 DARS1 NM_001349.4(DARS1):c.1493G>A (p.Arg498Gln) SNV Uncertain significance 1031971 GRCh37: 2:136664899-136664899
GRCh38: 2:135907329-135907329
15 DARS1 NM_001349.4(DARS1):c.484C>T (p.Pro162Ser) SNV Uncertain significance 735228 rs149170955 GRCh37: 2:136691500-136691500
GRCh38: 2:135933930-135933930

UniProtKB/Swiss-Prot genetic disease variations for Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity:

72
# Symbol AA change Variation ID SNP ID
1 DARS1 p.Met256Leu VAR_070038 rs886037635
2 DARS1 p.Ala274Val VAR_070039 rs369152939
3 DARS1 p.Asp367Tyr VAR_070040 rs370064817
4 DARS1 p.Arg460His VAR_070041 rs587776985
5 DARS1 p.Pro464Leu VAR_070042 rs148806569
6 DARS1 p.Arg487Cys VAR_070043 rs587776984
7 DARS1 p.Arg494Cys VAR_070044 rs147077598
8 DARS1 p.Arg494Gly VAR_070045 rs147077598

Expression for Hypomyelination with Brainstem and Spinal Cord Involvement and...

Search GEO for disease gene expression data for Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity.

Pathways for Hypomyelination with Brainstem and Spinal Cord Involvement and...

Pathways related to Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity according to KEGG:

36
# Name Kegg Source Accession
1 Aminoacyl-tRNA biosynthesis hsa00970

GO Terms for Hypomyelination with Brainstem and Spinal Cord Involvement and...

Sources for Hypomyelination with Brainstem and Spinal Cord Involvement and...

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
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