HLD11
MCID: LKD021
MIFTS: 37

Leukodystrophy, Hypomyelinating, 11 (HLD11)

Categories: Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Muscle diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Leukodystrophy, Hypomyelinating, 11

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 11:

Name: Leukodystrophy, Hypomyelinating, 11 57 73
Hypomyelinating Leukodystrophy 11 11 28 5 14
Hld11 57 11 73
4h Leukodystrophy 3 57 73
Leukodystrophy, Hypomyelinating, Type 11 38

Characteristics:


Inheritance:

Autosomal recessive 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
onset in first years of life
some patients may show deterioration with infections


Classifications:



Summaries for Leukodystrophy, Hypomyelinating, 11

OMIM®: 57 Hypomyelinating leukodystrophy-11 (HLD11) is an autosomal recessive neurologic disorder characterized by delayed psychomotor development and other neurologic features associated with hypomyelination on brain imaging. Some patients may have additional nonneurologic features, particularly dental abnormalities and possibly hypogonadotropic hypogonadism (summary by Thiffault et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080. (616494) (Updated 08-Dec-2022)

MalaCards based summary: Leukodystrophy, Hypomyelinating, 11, also known as hypomyelinating leukodystrophy 11, is related to cerebrooculofacioskeletal syndrome 2 and cerebellofaciodental syndrome. An important gene associated with Leukodystrophy, Hypomyelinating, 11 is POLR1C (RNA Polymerase I And III Subunit C), and among its related pathways/superpathways are RNA Polymerase III Transcription Initiation and Cytosolic sensors of pathogen-associated DNA. Affiliated tissues include brain and peripheral nerve, and related phenotypes are intellectual disability and spasticity

UniProtKB/Swiss-Prot: 73 An autosomal recessive neurologic disorder characterized by brain hypomyelination, delayed psychomotor development, intellectual disability, tremor and other neurologic symptoms. Some patients may additionally manifest non-neurologic features, particularly dental abnormalities and hypogonadotropic hypogonadism.

Disease Ontology: 11 A hypomyelinating leukodystrophy characterized by autosomal recessive inheritance of delayed psychomotor development and other neurologic features associated with hypomyelination that has material basis in homozygous or compound heterozygous mutation in the POLR1C gene on chromosome 6p21.

Related Diseases for Leukodystrophy, Hypomyelinating, 11

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
Leukodystrophy, Hypomyelinating, 18 Leukodystrophy, Hypomyelinating, 19, Transient Infantile
Leukodystrophy, Hypomyelinating, 20 Leukodystrophy, Hypomyelinating, 21
Leukodystrophy, Hypomyelinating, 22 Leukodystrophy, Hypomyelinating, 24

Diseases related to Leukodystrophy, Hypomyelinating, 11 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 24)
# Related Disease Score Top Affiliating Genes
1 cerebrooculofacioskeletal syndrome 2 10.1 POLR3B POLR3A
2 cerebellofaciodental syndrome 10.0 POLR3B POLR3A
3 boucher-neuhauser syndrome 10.0 POLR3B POLR3A
4 spastic paraplegia 25, autosomal recessive 10.0 TMEM63A POLR3A
5 polr3-related leukodystrophy 10.0 POLR3B POLR3A POLR1C
6 leukodystrophy, hypomyelinating, 6 10.0 POLR3B POLR3A
7 hypomyelinating leukoencephalopathy 9.9 POLR3B POLR3A HIKESHI
8 gordon holmes syndrome 9.9 POLR3B POLR3A
9 pelizaeus-merzbacher disease 9.9 POLR3B POLR3A HIKESHI
10 lissencephaly 6 9.9 TANGO2 EMC1
11 leukodystrophy, hypomyelinating, 4 9.8 TMEM63A POLR3A HIKESHI
12 dystonia 11, myoclonic 9.8 POLR3B POLR3A
13 leukodystrophy, hypomyelinating, 12 9.8 HIKESHI EIF2B3
14 spastic ataxia 8 9.7 POLR3B HIKESHI EIF2B3
15 cerebral degeneration 9.7 POLR3B POLR3A EIF2B3
16 leukodystrophy, hypomyelinating, 13 9.7 POLR3B HIKESHI EIF2B3
17 peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease 9.7 POLR3B HIKESHI EIF2B3
18 leukoencephalopathy with vanishing white matter 9.7 POLR3B POLR3A EIF2B3
19 treacher collins syndrome 3 9.6 TANGO2 POLR1C GSPT2 EMC1
20 leukodystrophy, hypomyelinating, 9 9.5 POLR3B POLR3A HIKESHI EIF2B3
21 leukodystrophy, hypomyelinating, 10 9.5 POLR3B POLR3A HIKESHI EIF2B3
22 hypomyelinating leukodystrophy 9.5 TMEM63A POLR3B POLR3A POLR1C HIKESHI
23 leukodystrophy 9.1 TMEM63A POLR3B POLR3A POLR1C HIKESHI EIF2B3
24 leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism 9.0 ZNF79 TMEM63A POLR3B POLR3A HIKESHI EIF2B3

Graphical network of the top 20 diseases related to Leukodystrophy, Hypomyelinating, 11:



Diseases related to Leukodystrophy, Hypomyelinating, 11

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 11

Human phenotypes related to Leukodystrophy, Hypomyelinating, 11:

30 (show all 14)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 30 Very rare (1%) HP:0001249
2 spasticity 30 Very rare (1%) HP:0001257
3 failure to thrive 30 Very rare (1%) HP:0001508
4 ataxia 30 Very rare (1%) HP:0001251
5 tremor 30 Very rare (1%) HP:0001337
6 global developmental delay 30 Very rare (1%) HP:0001263
7 abnormality of the dentition 30 Very rare (1%) HP:0000164
8 myoclonus 30 Very rare (1%) HP:0001336
9 myopia 30 Very rare (1%) HP:0000545
10 cerebellar atrophy 30 Very rare (1%) HP:0001272
11 hypoplasia of the corpus callosum 30 Very rare (1%) HP:0002079
12 cns hypomyelination 30 Very rare (1%) HP:0003429
13 delayed ability to walk 30 Very rare (1%) HP:0031936
14 leukodystrophy 30 HP:0002415

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Neurologic Central Nervous System:
intellectual disability
tremor
leukodystrophy
thin corpus callosum
delayed psychomotor development
more
Head And Neck Teeth:
dental abnormalities (in some patients)

Head And Neck Eyes:
myopia (in some patients)

Head And Neck Head:
head titubations (in some patients)

Clinical features from OMIM®:

616494 (Updated 08-Dec-2022)

GenomeRNAi Phenotypes related to Leukodystrophy, Hypomyelinating, 11 according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-197 9.23 POLR1C POLR3B
2 Increased shRNA abundance (Z-score > 2) GR00366-A-216 9.23 POLR3B
3 Increased shRNA abundance (Z-score > 2) GR00366-A-23 9.23 POLR1C
4 Increased shRNA abundance (Z-score > 2) GR00366-A-26 9.23 POLR1C
5 Increased shRNA abundance (Z-score > 2) GR00366-A-94 9.23 POLR1C
6 Increased shRNA abundance (Z-score > 2) GR00366-A-99 9.23 POLR1C POLR3B

Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 11

Search Clinical Trials, NIH Clinical Center for Leukodystrophy, Hypomyelinating, 11

Genetic Tests for Leukodystrophy, Hypomyelinating, 11

Genetic tests related to Leukodystrophy, Hypomyelinating, 11:

# Genetic test Affiliating Genes
1 Hypomyelinating Leukodystrophy 11 28 POLR1C

Anatomical Context for Leukodystrophy, Hypomyelinating, 11

Organs/tissues related to Leukodystrophy, Hypomyelinating, 11:

MalaCards : Brain
ODiseA: Peripheral Nerve, Brain

Publications for Leukodystrophy, Hypomyelinating, 11

Articles related to Leukodystrophy, Hypomyelinating, 11:

# Title Authors PMID Year
1
Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III. 57 5
26151409 2015
2
Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C. 57
33005949 2021
3
Clinical spectrum of POLR3-related leukodystrophy caused by biallelic POLR1C pathogenic variants. 5
32042905 2019
4
Lessons learned from additional research analyses of unsolved clinical exome cases. 5
28327206 2017
5
Epididymal sarcoidosis: a report of two cases and a review of the literature. 5
610060 1977

Variations for Leukodystrophy, Hypomyelinating, 11

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 11:

5 (show all 37)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 POLR1C NM_203290.4(POLR1C):c.69+1G>A SNV Pathogenic
635139 rs1582177745 GRCh37: 6:43484917-43484917
GRCh38: 6:43517179-43517179
2 POLR1C NM_203290.4(POLR1C):c.70-1G>A SNV Pathogenic
280457 rs886041661 GRCh37: 6:43485043-43485043
GRCh38: 6:43517305-43517305
3 POLR1C NM_203290.4(POLR1C):c.79A>G (p.Thr27Ala) SNV Pathogenic
211929 rs144054843 GRCh37: 6:43485053-43485053
GRCh38: 6:43517315-43517315
4 POLR1C NM_203290.4(POLR1C):c.313A>T (p.Ile105Phe) SNV Pathogenic
635141 rs770637715 GRCh37: 6:43487507-43487507
GRCh38: 6:43519769-43519769
5 POLR1C NM_203290.4(POLR1C):c.322C>T (p.His108Tyr) SNV Pathogenic
635142 rs1015942660 GRCh37: 6:43487516-43487516
GRCh38: 6:43519778-43519778
6 POLR1C NM_203290.4(POLR1C):c.325C>T (p.Arg109Cys) SNV Pathogenic
635143 rs1255115751 GRCh37: 6:43487519-43487519
GRCh38: 6:43519781-43519781
7 POLR1C NM_203290.4(POLR1C):c.349G>C (p.Ala117Pro) SNV Pathogenic
635144 rs1582181247 GRCh37: 6:43487543-43487543
GRCh38: 6:43519805-43519805
8 POLR1C NM_203290.4(POLR1C):c.502G>A (p.Val168Met) SNV Pathogenic
635147 rs773388338 GRCh37: 6:43487923-43487923
GRCh38: 6:43520185-43520185
9 POLR1C NM_203290.4(POLR1C):c.616del (p.Gln206fs) DEL Pathogenic
Pathogenic
635148 rs1156407486 GRCh37: 6:43488125-43488125
GRCh38: 6:43520387-43520387
10 POLR1C NM_203290.4(POLR1C):c.699C>G (p.Tyr233Ter) SNV Pathogenic
280857 rs763593155 GRCh37: 6:43488406-43488406
GRCh38: 6:43520668-43520668
11 POLR1C NM_203290.4(POLR1C):c.835C>T (p.Arg279Trp) SNV Pathogenic
30815 rs141156009 GRCh37: 6:43488699-43488699
GRCh38: 6:43520961-43520961
12 POLR1C NM_203290.4(POLR1C):c.916_920del (p.Tyr306fs) DEL Pathogenic
635151 rs767639108 GRCh37: 6:43488778-43488782
GRCh38: 6:43521040-43521044
13 POLR1C NM_203290.4(POLR1C):c.938C>T (p.Thr313Met) SNV Pathogenic
635152 rs181576159 GRCh37: 6:43488935-43488935
GRCh38: 6:43521197-43521197
14 POLR1C NM_203290.4(POLR1C):c.733G>A (p.Val245Met) SNV Pathogenic
635149 rs772343871 GRCh37: 6:43488440-43488440
GRCh38: 6:43520702-43520702
15 POLR1C NM_203290.4(POLR1C):c.221A>G (p.Asn74Ser) SNV Pathogenic
204587 rs371802902 GRCh37: 6:43487150-43487150
GRCh38: 6:43519412-43519412
16 POLR1C NM_203290.4(POLR1C):c.95A>T (p.Asn32Ile) SNV Pathogenic
204588 rs796052124 GRCh37: 6:43485069-43485069
GRCh38: 6:43517331-43517331
17 POLR1C NM_203290.4(POLR1C):c.436T>C (p.Cys146Arg) SNV Pathogenic
204589 rs796052125 GRCh37: 6:43487857-43487857
GRCh38: 6:43520119-43520119
18 POLR1C NM_203290.4(POLR1C):c.880AAG[1] (p.Lys295del) MICROSAT Pathogenic
204590 rs875989826 GRCh37: 6:43488744-43488746
GRCh38: 6:43521006-43521008
19 POLR1C NM_203290.4(POLR1C):c.77C>T (p.Thr26Ile) SNV Pathogenic
204591 rs796052126 GRCh37: 6:43485051-43485051
GRCh38: 6:43517313-43517313
20 POLR1C NM_203290.4(POLR1C):c.326G>A (p.Arg109His) SNV Pathogenic
204592 rs796052127 GRCh37: 6:43487520-43487520
GRCh38: 6:43519782-43519782
21 POLR1C NM_203290.4(POLR1C):c.281T>C (p.Val94Ala) SNV Pathogenic
635140 rs1305006253 GRCh37: 6:43487475-43487475
GRCh38: 6:43519737-43519737
22 POLR1C NM_203290.4(POLR1C):c.395G>A (p.Gly132Asp) SNV Pathogenic
635145 rs201320592 GRCh37: 6:43487816-43487816
GRCh38: 6:43520078-43520078
23 POLR1C NM_203290.4(POLR1C):c.461_462del (p.Lys154fs) DEL Pathogenic
635146 rs770857344 GRCh37: 6:43487881-43487882
GRCh38: 6:43520143-43520144
24 POLR1C NM_203290.4(POLR1C):c.572G>A (p.Arg191Gln) SNV Pathogenic
285658 rs373046018 GRCh37: 6:43488082-43488082
GRCh38: 6:43520344-43520344
25 POLR1C NM_203290.4(POLR1C):c.785T>C (p.Ile262Thr) SNV Pathogenic
635150 rs751006626 GRCh37: 6:43488492-43488492
GRCh38: 6:43520754-43520754
26 POLR1C NM_203290.4(POLR1C):c.970G>A (p.Glu324Lys) SNV Pathogenic
635153 rs1582184344 GRCh37: 6:43488967-43488967
GRCh38: 6:43521229-43521229
27 POLR1C NM_203290.4(POLR1C):c.836G>A (p.Arg279Gln) SNV Pathogenic
30811 rs191582628 GRCh37: 6:43488700-43488700
GRCh38: 6:43520962-43520962
28 POLR1C NM_203290.4(POLR1C):c.614del (p.Gly205fs) DEL Pathogenic
375403 rs1057519456 GRCh37: 6:43488123-43488123
GRCh38: 6:43520385-43520385
29 POLR1C NM_203290.4(POLR1C):c.525del (p.Thr174_Trp175insTer) DEL Pathogenic
225445 rs780663139 GRCh37: 6:43488034-43488034
GRCh38: 6:43520296-43520296
30 POLR1C NM_203290.4(POLR1C):c.88C>T (p.Pro30Ser) SNV Pathogenic/Likely Pathogenic
Uncertain Significance
375402 rs1057519455 GRCh37: 6:43485062-43485062
GRCh38: 6:43517324-43517324
31 POLR1C NM_203290.4(POLR1C):c.208dup (p.Ala70fs) DUP Likely Pathogenic
1676483 GRCh37:
GRCh38:
32 POLR1C NM_203290.4(POLR1C):c.908G>A (p.Arg303Gln) SNV Likely Pathogenic
1308109 GRCh37: 6:43488772-43488772
GRCh38: 6:43521034-43521034
33 POLR1C NM_203290.4(POLR1C):c.364T>A (p.Phe122Ile) SNV Likely Pathogenic
548465 rs1554131502 GRCh37: 6:43487558-43487558
GRCh38: 6:43519820-43519820
34 POLR1C NM_203290.4(POLR1C):c.193A>G (p.Met65Val) SNV Conflicting Interpretations Of Pathogenicity
356872 rs141471029 GRCh37: 6:43487122-43487122
GRCh38: 6:43519384-43519384
35 POLR1C NM_203290.4(POLR1C):c.32G>A (p.Arg11Gln) SNV Uncertain Significance
1344573 GRCh37: 6:43484879-43484879
GRCh38: 6:43517141-43517141
36 POLR1C NM_203290.4(POLR1C):c.110A>G (p.Asp37Gly) SNV Uncertain Significance
522737 rs1004141332 GRCh37: 6:43485084-43485084
GRCh38: 6:43517346-43517346
37 POLR1C NM_203290.4(POLR1C):c.421C>T (p.Arg141Cys) SNV Uncertain Significance
724886 rs148385032 GRCh37: 6:43487842-43487842
GRCh38: 6:43520104-43520104

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 11:

73 (show all 11)
# Symbol AA change Variation ID SNP ID
1 POLR1C p.Thr26Ile VAR_074655 rs796052126
2 POLR1C p.Asn32Ile VAR_074656 rs796052124
3 POLR1C p.Met65Val VAR_074657 rs141471029
4 POLR1C p.Asn74Ser VAR_074658 rs371802902
5 POLR1C p.Val94Ala VAR_074659 rs1305006253
6 POLR1C p.Arg109His VAR_074660 rs796052127
7 POLR1C p.Gly132Asp VAR_074661 rs201320592
8 POLR1C p.Cys146Arg VAR_074662 rs796052125
9 POLR1C p.Arg191Gln VAR_074663 rs373046018
10 POLR1C p.Ile262Thr VAR_074664 rs751006626
11 POLR1C p.Glu324Lys VAR_074666 rs1582184344

Expression for Leukodystrophy, Hypomyelinating, 11

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 11.

Pathways for Leukodystrophy, Hypomyelinating, 11

Pathways related to Leukodystrophy, Hypomyelinating, 11 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.88 POLR3B POLR3A POLR1C
2
Show member pathways
11.73 POLR3B POLR3A POLR1C
3
Show member pathways
11.29 POLR3B POLR3A POLR1C
4
Show member pathways
11.19 GSPT2 EIF2B3
5 10.73 POLR3B POLR3A POLR1C

GO Terms for Leukodystrophy, Hypomyelinating, 11

Cellular components related to Leukodystrophy, Hypomyelinating, 11 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-directed RNA polymerase complex GO:0000428 9.13 POLR3B POLR3A POLR1C
2 RNA polymerase III complex GO:0005666 9.1 POLR3B POLR3A POLR1C

Biological processes related to Leukodystrophy, Hypomyelinating, 11 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of interferon-beta production GO:0032728 9.26 POLR3B POLR3A
2 DNA-templated transcription GO:0006351 9.02 POLR3B POLR3A POLR1C

Molecular functions related to Leukodystrophy, Hypomyelinating, 11 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleotidyltransferase activity GO:0016779 9.26 POLR3B POLR3A EIF2B3
2 DNA-directed 5'-3' RNA polymerase activity GO:0003899 9.1 POLR3B POLR3A POLR1C

Sources for Leukodystrophy, Hypomyelinating, 11

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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