HLD9
MCID: LKD016
MIFTS: 24

Leukodystrophy, Hypomyelinating, 9 (HLD9)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Leukodystrophy, Hypomyelinating, 9

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 9:

Name: Leukodystrophy, Hypomyelinating, 9 58 76 30 6 74
Hld9 58 12 76
Rars-Related Autosomal Recessive Hypomyelinating Leukodystrophy 12 60
Leukodystrophy, Hypomyelinating, Type 9 41
Hypomyelinating Leukodystrophy 9 12

Characteristics:

Orphanet epidemiological data:

60
rars-related autosomal recessive hypomyelinating leukodystrophy
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset in the first year of life
six patients from 5 families have been reported (last curated november 2018)


HPO:

33
leukodystrophy, hypomyelinating, 9:
Onset and clinical course variable expressivity
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Leukodystrophy, Hypomyelinating, 9

OMIM : 58 Hypomyelinating leukodystrophy-9 is an autosomal recessive neurologic disorder characterized by onset of delayed psychomotor development, spasticity, and nystagmus in the first year of life. Additional neurologic features such as ataxia and abnormal movements may also occur. Brain imaging shows diffuse hypomyelination affecting all regions of the brain (summary by Wolf et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080. (616140)

MalaCards based summary : Leukodystrophy, Hypomyelinating, 9, is also known as hld9, and has symptoms including ataxia and action tremor. An important gene associated with Leukodystrophy, Hypomyelinating, 9 is RARS (Arginyl-TRNA Synthetase). Affiliated tissues include brain and eye, and related phenotypes are nystagmus and hyperreflexia

Disease Ontology : 12 A hypomyelinating leukodystrophy characterized by delayed psychomotor development, spasticity, and nystagmus starting in the first year of life that has material basis in compound heterozygous mutation in the RARS gene on chromosome 5q34.

UniProtKB/Swiss-Prot : 76 Leukodystrophy, hypomyelinating, 9: An autosomal recessive neurodegenerative disorder characterized by delayed psychomotor development, severe spasticity, nystagmus, and ataxia associated with diffuse hypomyelination apparent on brain MRI.

Related Diseases for Leukodystrophy, Hypomyelinating, 9

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 9

Human phenotypes related to Leukodystrophy, Hypomyelinating, 9:

60 33 (show all 31)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 60 33 frequent (33%) Frequent (79-30%) HP:0000639
2 hyperreflexia 60 33 frequent (33%) Frequent (79-30%) HP:0001347
3 global developmental delay 60 33 frequent (33%) Frequent (79-30%) HP:0001263
4 intellectual disability, mild 60 33 frequent (33%) Frequent (79-30%) HP:0001256
5 developmental stagnation 60 33 frequent (33%) Frequent (79-30%) HP:0007281
6 dysmetria 60 33 frequent (33%) Frequent (79-30%) HP:0001310
7 intention tremor 60 33 frequent (33%) Frequent (79-30%) HP:0002080
8 dystonia 60 33 frequent (33%) Frequent (79-30%) HP:0001332
9 difficulty walking 60 33 frequent (33%) Frequent (79-30%) HP:0002355
10 hyperintensity of cerebral white matter on mri 60 33 frequent (33%) Frequent (79-30%) HP:0030890
11 lower limb spasticity 60 33 frequent (33%) Frequent (79-30%) HP:0002061
12 hypoplasia of the corpus callosum 60 33 frequent (33%) Frequent (79-30%) HP:0002079
13 lower limb hypertonia 60 33 frequent (33%) Frequent (79-30%) HP:0006895
14 poor head control 60 33 frequent (33%) Frequent (79-30%) HP:0002421
15 progressive extrapyramidal movement disorder 60 33 frequent (33%) Frequent (79-30%) HP:0007153
16 infantile axial hypotonia 60 33 frequent (33%) Frequent (79-30%) HP:0009062
17 poor eye contact 60 33 frequent (33%) Frequent (79-30%) HP:0000817
18 cerebral hypomyelination 60 33 frequent (33%) Frequent (79-30%) HP:0006808
19 microcephaly 60 33 occasional (7.5%) Occasional (29-5%) HP:0000252
20 vomiting 60 33 occasional (7.5%) Occasional (29-5%) HP:0002013
21 increased serum lactate 60 33 occasional (7.5%) Occasional (29-5%) HP:0002151
22 pseudobulbar paralysis 60 33 occasional (7.5%) Occasional (29-5%) HP:0007024
23 diffuse cerebral atrophy 60 33 occasional (7.5%) Occasional (29-5%) HP:0002506
24 absent smooth pursuit 60 33 occasional (7.5%) Occasional (29-5%) HP:0007179
25 dysarthria 60 33 Frequent (79-30%) HP:0001260
26 intellectual disability 33 HP:0001249
27 ataxia 60 Frequent (79-30%)
28 spasticity 33 HP:0001257
29 abnormality of extrapyramidal motor function 33 HP:0002071
30 focal seizures 60 Occasional (29-5%)
31 leukodystrophy 33 HP:0002415

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
nystagmus
poor smooth pursuit
poor visual fixation (1 patient)

Head And Neck Head:
microcephaly (1 patient)

Neurologic Central Nervous System:
ataxia
dysarthria
hyperreflexia
dysmetria
intention tremor
more
Muscle Soft Tissue:
hypertonicity of the lower limbs

Clinical features from OMIM:

616140

UMLS symptoms related to Leukodystrophy, Hypomyelinating, 9:


ataxia, action tremor

Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 9

Search Clinical Trials , NIH Clinical Center for Leukodystrophy, Hypomyelinating, 9

Genetic Tests for Leukodystrophy, Hypomyelinating, 9

Genetic tests related to Leukodystrophy, Hypomyelinating, 9:

# Genetic test Affiliating Genes
1 Leukodystrophy, Hypomyelinating, 9 30 RARS

Anatomical Context for Leukodystrophy, Hypomyelinating, 9

MalaCards organs/tissues related to Leukodystrophy, Hypomyelinating, 9:

42
Brain, Eye

Publications for Leukodystrophy, Hypomyelinating, 9

Variations for Leukodystrophy, Hypomyelinating, 9

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 9:

76
# Symbol AA change Variation ID SNP ID
1 RARS p.Asp2Gly VAR_072666 rs672601372
2 RARS p.Arg512Gln VAR_072667 rs369398935

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 9:

6 (show all 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 RARS NM_002887.3(RARS): c.5A> G (p.Asp2Gly) single nucleotide variant Pathogenic rs672601372 GRCh38 Chromosome 5, 168486503: 168486503
2 RARS NM_002887.3(RARS): c.5A> G (p.Asp2Gly) single nucleotide variant Pathogenic rs672601372 GRCh37 Chromosome 5, 167913508: 167913508
3 RARS NM_002887.3(RARS): c.45+1G> T single nucleotide variant Pathogenic rs672601373 GRCh38 Chromosome 5, 168486544: 168486544
4 RARS NM_002887.3(RARS): c.45+1G> T single nucleotide variant Pathogenic rs672601373 GRCh37 Chromosome 5, 167913549: 167913549
5 RARS NM_002887.3(RARS): c.96_97delTG (p.Cys32Trpfs) deletion Pathogenic rs672601374 GRCh37 Chromosome 5, 167915657: 167915658
6 RARS NM_002887.3(RARS): c.96_97delTG (p.Cys32Trpfs) deletion Pathogenic rs672601374 GRCh38 Chromosome 5, 168488652: 168488653
7 RARS NM_002887.3(RARS): c.1A> G (p.Met1Val) single nucleotide variant Pathogenic rs672601375 GRCh38 Chromosome 5, 168486499: 168486499
8 RARS NM_002887.3(RARS): c.1A> G (p.Met1Val) single nucleotide variant Pathogenic rs672601375 GRCh37 Chromosome 5, 167913504: 167913504
9 RARS NM_002887.3(RARS): c.1535G> A (p.Arg512Gln) single nucleotide variant Pathogenic rs369398935 GRCh38 Chromosome 5, 168516860: 168516860
10 RARS NM_002887.3(RARS): c.1535G> A (p.Arg512Gln) single nucleotide variant Pathogenic rs369398935 GRCh37 Chromosome 5, 167943865: 167943865
11 RARS NM_002887.3(RARS): c.1367C> T (p.Ser456Leu) single nucleotide variant Pathogenic rs139644798 GRCh38 Chromosome 5, 168510601: 168510601
12 RARS NM_002887.3(RARS): c.1367C> T (p.Ser456Leu) single nucleotide variant Pathogenic rs139644798 GRCh37 Chromosome 5, 167937606: 167937606
13 RARS NM_002887.3(RARS): c.1846_1847delTA (p.Tyr616Leufs) deletion Pathogenic rs1064792894 GRCh38 Chromosome 5, 168518035: 168518036
14 RARS NM_002887.3(RARS): c.1846_1847delTA (p.Tyr616Leufs) deletion Pathogenic rs1064792894 GRCh37 Chromosome 5, 167945040: 167945041

Expression for Leukodystrophy, Hypomyelinating, 9

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 9.

Pathways for Leukodystrophy, Hypomyelinating, 9

GO Terms for Leukodystrophy, Hypomyelinating, 9

Sources for Leukodystrophy, Hypomyelinating, 9

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75 UMLS via Orphanet
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