Leukodystrophy, Hypomyelinating, 10 disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

MCID: LKD020 MIFTS: 26	Leukodystrophy, Hypomyelinating, 10 Categories: Genetic diseases, Neuronal diseases, Fetal diseases, Rare diseases, Eye diseases
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Aliases & Classifications for Leukodystrophy, Hypomyelinating, 10

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 10:

Name: Leukodystrophy, Hypomyelinating, 10 ⁵⁷ ⁷⁵ ⁶

Hld10 ⁵⁷ ¹² ⁷⁵

Hypomyelinating Leukodystrophy 10 ¹² ¹⁵

Pycr2-Related Microcephaly-Progressive Leukoencephalopathy ⁵⁹

Leukodystrophy, Hypomyelinating, Type 10 ⁴⁰

Characteristics:

OMIM:

⁵⁷

Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset at birth or in first months of life
death often occurs in first decade

HPO:

³²

leukodystrophy, hypomyelinating, 10:
Onset and clinical course progressive
Inheritance autosomal recessive inheritance

Classifications:

MalaCards categories:
Global: Genetic diseases Fetal diseases Rare diseases
Anatomical: Neuronal diseases Eye diseases

See all MalaCards categories (disease lists)

Orphanet: ⁵⁹

Rare neurological diseases

Developmental anomalies during embryogenesis

External Ids:

OMIM ⁵⁷ 616420

Disease Ontology ¹² DOID:0060788

Orphanet ⁵⁹ ORPHA481152

MedGen ⁴² C4225332 CN231317

MeSH ⁴⁴ D020279

SNOMED-CT via HPO ⁶⁹ 258211005 103276001 15188001 more

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Summaries for Leukodystrophy, Hypomyelinating, 10

OMIM : ⁵⁷ Hypomyelinating leukodystrophy-10 is an autosomal recessive neurologic disorder characterized by postnatal progressive microcephaly, severely delayed psychomotor development, and hypomyelination on brain imaging (summary by Nakayama et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080. (616420)

MalaCards based summary : Leukodystrophy, Hypomyelinating, 10, is also known as hld10. An important gene associated with Leukodystrophy, Hypomyelinating, 10 is PYCR2 (Pyrroline-5-Carboxylate Reductase 2), and among its related pathways/superpathways are Viral mRNA Translation and Amino acid synthesis and interconversion (transamination). Affiliated tissues include brain and skeletal muscle, and related phenotypes are malar flattening and low-set ears

UniProtKB/Swiss-Prot : ⁷⁵ Leukodystrophy, hypomyelinating, 10: An autosomal recessive neurologic disorder characterized by postnatal microcephaly, severely delayed psychomotor development, hypomyelination, and reduced cerebral white-matter volume.

Disease Ontology : ¹² A hypomyelinating leukodystrophy characterized by autosomal recessive inheritance of progressive postnatal microcephaly, severely delayed psychomotor development and hypomyelination that has material basis in homozygous mutation in the PYCR2 gene on chromosome 1q42.

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Related Diseases for Leukodystrophy, Hypomyelinating, 10

Diseases in the Hypomyelinating Leukodystrophy family:

Leukodystrophy, Hypomyelinating, 3	Leukodystrophy, Hypomyelinating, 2
Leukodystrophy, Hypomyelinating, 5	Leukodystrophy, Hypomyelinating, 4
Leukodystrophy, Hypomyelinating, 6	Leukodystrophy, Hypomyelinating, 9
Leukodystrophy, Hypomyelinating, 10	Leukodystrophy, Hypomyelinating, 11
Leukodystrophy, Hypomyelinating, 12	Leukodystrophy, Hypomyelinating, 13
Leukodystrophy, Hypomyelinating, 14	Leukodystrophy, Hypomyelinating, 15
Leukodystrophy, Hypomyelinating, 16	Leukodystrophy, Hypomyelinating, 17

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Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 10

Symptoms via clinical synopsis from OMIM:

⁵⁷

Head And Neck Ears:
low-set ears
hearing loss
large malformed ears

Growth Other:
failure to thrive
poor overall growth

Head And Neck Face:
smooth philtrum
long philtrum
triangular face
malar hypoplasia
bitemporal narrowing
more

Head And Neck Eyes:
downslanting palpebral fissures
nystagmus (in some patients)
upslanting palpebral fissures

Head And Neck Mouth:
full lips

Skeletal Feet:
hyperextensibility of the ankles

Neurologic Central Nervous System:
spasticity
hyperreflexia
inability to walk
cerebral atrophy
hypomyelination
more

Head And Neck Nose:
short nose
bulbous nose
upturned nose

Skeletal Hands:
arachnodactyly
hyperextensibility of the wrists

Muscle Soft Tissue:
muscle wasting
truncal hypotonia

Head And Neck Head:
microcephaly, postnatal, progressive (up to -7.7 sd)

Clinical features from OMIM:

616420

Human phenotypes related to Leukodystrophy, Hypomyelinating, 10:

³² (show all 30)

#	Description	HPO Frequency	HPO Source Accession
1	malar flattening ³²		HP:0000272
2	low-set ears ³²		HP:0000369
3	nystagmus ³²	occasional (7.5%)	HP:0000639
4	seizures ³²	occasional (7.5%)	HP:0001250
5	spasticity ³²		HP:0001257
6	hyperreflexia ³²		HP:0001347
7	failure to thrive ³²		HP:0001508
8	hearing impairment ³²		HP:0000365
9	global developmental delay ³²		HP:0001263
10	short nose ³²		HP:0003196
11	thick vermilion border ³²		HP:0012471
12	smooth philtrum ³²		HP:0000319
13	anteverted nares ³²		HP:0000463
14	skeletal muscle atrophy ³²		HP:0003202
15	long philtrum ³²		HP:0000343
16	absent speech ³²		HP:0001344
17	babinski sign ³²		HP:0003487
18	inability to walk ³²		HP:0002540
19	cerebral cortical atrophy ³²		HP:0002120
20	arachnodactyly ³²		HP:0001166
21	downslanted palpebral fissures ³²		HP:0000494
22	upslanted palpebral fissure ³²		HP:0000582
23	bulbous nose ³²		HP:0000414
24	triangular face ³²		HP:0000325
25	hypoplasia of the corpus callosum ³²		HP:0002079
26	leukodystrophy ³²		HP:0002415
27	cns hypomyelination ³²		HP:0003429
28	narrow forehead ³²		HP:0000341
29	muscular hypotonia of the trunk ³²		HP:0008936
30	progressive microcephaly ³²		HP:0000253

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Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 10

Search Clinical Trials , NIH Clinical Center for Leukodystrophy, Hypomyelinating, 10

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Genetic Tests for Leukodystrophy, Hypomyelinating, 10

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Anatomical Context for Leukodystrophy, Hypomyelinating, 10

MalaCards organs/tissues related to Leukodystrophy, Hypomyelinating, 10:

⁴¹

Brain, Skeletal Muscle

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Publications for Leukodystrophy, Hypomyelinating, 10

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Genes for Leukodystrophy, Hypomyelinating, 10

Genes related to Leukodystrophy, Hypomyelinating, 10 (1 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubmedIds
1	PYCR2	Pyrroline-5-Carboxylate Reductase 2	Protein Coding	1587.26	Molecular basis known ⁵⁷ Pathogenic ⁶ Causative germline mutation (loss of function) ⁵⁹ Causative variation ⁷⁵ DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Variants (show sections)	25865492 27130255
2	MIR6741	MicroRNA 6741	RNA Gene	7.99	GeneCards inferred via : Variants (show sections)

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Variations for Leukodystrophy, Hypomyelinating, 10

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 10:

⁷⁵

#	Symbol	AA change	Variation ID	SNP ID
1	PYCR2	p.Arg119Cys	VAR_074608	rs372781135
2	PYCR2	p.Arg251Cys	VAR_074609	rs876657403

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 10:

⁶

(show all 16)

#	Gene	Variation	Type	Significance	SNP ID	Assembly	Location
1	PYCR2	NM_013328.3(PYCR2): c.355C> T (p.Arg119Cys)	single nucleotide variant	Pathogenic	rs372781135	GRCh37	Chromosome 1, 226109743: 226109743
2	PYCR2	NM_013328.3(PYCR2): c.355C> T (p.Arg119Cys)	single nucleotide variant	Pathogenic	rs372781135	GRCh38	Chromosome 1, 225922043: 225922043
3	PYCR2	NM_013328.3(PYCR2): c.751C> T (p.Arg251Cys)	single nucleotide variant	Pathogenic	rs876657403	GRCh37	Chromosome 1, 226108954: 226108954
4	PYCR2	NM_013328.3(PYCR2): c.751C> T (p.Arg251Cys)	single nucleotide variant	Pathogenic	rs876657403	GRCh38	Chromosome 1, 225921254: 225921254
5	PYCR2	NM_013328.3(PYCR2): c.796C> T (p.Arg266Ter)	single nucleotide variant	Pathogenic	rs886037931	GRCh38	Chromosome 1, 225921209: 225921209
6	PYCR2	NM_013328.3(PYCR2): c.796C> T (p.Arg266Ter)	single nucleotide variant	Pathogenic	rs886037931	GRCh37	Chromosome 1, 226108909: 226108909
7	PYCR2	NM_013328.3(PYCR2): c.773T> C (p.Val258Ala)	single nucleotide variant	Pathogenic	rs886037932	GRCh38	Chromosome 1, 225921232: 225921232
8	PYCR2	NM_013328.3(PYCR2): c.773T> C (p.Val258Ala)	single nucleotide variant	Pathogenic	rs886037932	GRCh37	Chromosome 1, 226108932: 226108932
9	PYCR2	NM_013328.3(PYCR2): c.595C> T (p.Arg199Trp)	single nucleotide variant	Pathogenic	rs758595075	GRCh38	Chromosome 1, 225921590: 225921590
10	PYCR2	NM_013328.3(PYCR2): c.595C> T (p.Arg199Trp)	single nucleotide variant	Pathogenic	rs758595075	GRCh37	Chromosome 1, 226109290: 226109290
11	PYCR2	NM_013328.3(PYCR2): c.694T> G (p.Cys232Gly)	single nucleotide variant	Pathogenic	rs886037933	GRCh38	Chromosome 1, 225921311: 225921311
12	PYCR2	NM_013328.3(PYCR2): c.694T> G (p.Cys232Gly)	single nucleotide variant	Pathogenic	rs886037933	GRCh37	Chromosome 1, 226109011: 226109011
13	PYCR2	NM_013328.3(PYCR2): c.758_759insCT (p.Leu254Cysfs)	insertion	Pathogenic	rs886043378	GRCh37	Chromosome 1, 226108946: 226108947
14	PYCR2	NM_013328.3(PYCR2): c.758_759insCT (p.Leu254Cysfs)	insertion	Pathogenic	rs886043378	GRCh38	Chromosome 1, 225921246: 225921247
15	PYCR2	NM_013328.3(PYCR2): c.139-2A> C	single nucleotide variant	Likely pathogenic		GRCh37	Chromosome 1, 226110085: 226110085
16	PYCR2	NM_013328.3(PYCR2): c.139-2A> C	single nucleotide variant	Likely pathogenic		GRCh38	Chromosome 1, 225922385: 225922385

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Expression for Leukodystrophy, Hypomyelinating, 10

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 10.

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Pathways for Leukodystrophy, Hypomyelinating, 10

Pathways related to Leukodystrophy, Hypomyelinating, 10 according to GeneCards Suite gene sharing:

#	Super pathways	Score	Top Affiliating Genes
1	Viral mRNA Translation ⁶⁶ Show member pathways Cap-dependent Translation Initiation ⁶⁶ CFTR translational fidelity (class I mutations) ²² Cysteine formation from homocysteine ⁶⁶ Cytoplasmic Ribosomal Proteins ¹ Eukaryotic Translation Elongation ⁶⁶ Eukaryotic Translation Initiation ⁶⁶ Eukaryotic Translation Termination ⁶⁶ Formation of a pool of free 40S subunits ⁶⁶ glutathione redox reactions II ¹ GTP hydrolysis and joining of the 60S ribosomal subunit ⁶⁶ L13a-mediated translational silencing of Ceruloplasmin expression ⁶⁶ Metabolism of amino acids and derivatives ⁶⁶ Metabolism of ingested H2SeO4 and H2SeO3 into H2Se ⁶⁶ Metabolism of ingested MeSeO2H into MeSeH ⁶⁶ Metabolism of ingested SeMet, Sec, MeSec into H2Se ⁶⁶ Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) ⁶⁶ Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) ⁶⁶ Nonsense-Mediated Decay (NMD) ⁶⁶ Peptide chain elongation ⁶⁶ Ribosome ³⁷ Selenoamino acid metabolism ⁶⁶ Selenocysteine synthesis ⁶⁶ SRP-dependent cotranslational protein targeting to membrane ⁶⁶ sulfate activation for sulfonation ¹ Translation ⁶⁶	12.36	MIR6741 PYCR2
2	Amino acid synthesis and interconversion (transamination) ⁶⁶ Show member pathways asparagine biosynthesis ¹ Serine biosynthesis ⁶⁶	10.24	MIR6741 PYCR2

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GO Terms for Leukodystrophy, Hypomyelinating, 10

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Sources for Leukodystrophy, Hypomyelinating, 10

¹ BioSystems

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⁷¹ TGDB

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⁷⁵ UniProtKB/Swiss-Prot

⁷⁶ Wikipedia