MCID: LKD018
MIFTS: 27

Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism

Categories: Genetic diseases, Neuronal diseases

Aliases & Classifications for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia...

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism:

Name: Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism 57 75 13 73
Hld8 57 12 75
Hypomyelinating Leukodystrophy 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism 29 6
Hypomyelinating Leukodystrophy 8 with or Without Oligodontia and-or Hypogonadotropic Hypogonadism 12 15
Leukodystrophy, Hypomyelinating, Type 8, with/without Oligodontia and/or Hypogonadotropic Hypogonadism 40

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable phenotype
slowly progressive or nonprogressive
onset in early childhood (2 to 4 years)


HPO:

32
leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia...

OMIM : 57 Hypomyelinating leukodystrophy-8 is an autosomal recessive neurologic disorder characterized by early childhood onset of cerebellar ataxia and mild intellectual disabilities associated with diffuse hypomyelination apparent on brain MRI. Variable features include oligodontia and/or hypogonadotropic hypogonadism (summary by Tetreault et al., 2011). See also HLD7 (607694), which has similar features and is caused by mutation in the POLR3A gene (614258) on chromosome 10q22. The POLR3A and POLR3B genes encode the 2 largest subunits of RNA polymerase III. For a general phenotypic description and a discussion of genetic heterogeneity of hypomyelinating leukodystrophy, see 312080. (614381)

MalaCards based summary : Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism, also known as hld8, is related to pol iii-related leukodystrophies and leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, and has symptoms including cerebellar ataxia, tremor and dysdiadochokinesis. An important gene associated with Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism is POLR3B (RNA Polymerase III Subunit B). Affiliated tissues include brain, and related phenotypes are hypogonadotrophic hypogonadism and myopia

Disease Ontology : 12 A hypomyelinating leukodystrophy characterized by autosomal recessive inheritance of early childhood onset of cerebellar ataxia, mild intellectual disabilities associated with diffuse hypomyelination and variable development of oligodontia and/or hypogonadotropic hypogonadism that has material basis in compound heterozygous mutation in the POLR3B gene on chromosome 12q23.

UniProtKB/Swiss-Prot : 75 Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism: An autosomal recessive neurodegenerative disorder characterized by early childhood onset of cerebellar ataxia and mild intellectual disabilities associated with diffuse hypomyelination apparent on brain MRI. Variable features include oligodontia and/or hypogonadotropic hypogonadism.

Related Diseases for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia...

Diseases related to Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 pol iii-related leukodystrophies 11.8
2 leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism 11.0
3 leukodystrophy, hypomyelinating, 13 9.0 CYP2D6 LMOD1

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia...

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus
myopia
abnormal smooth pursuit
vertical gaze limitation

Growth Height:
short stature

Abdomen Gastrointestinal:
dysphagia (1 patient)

Neurologic Central Nervous System:
dysarthria
tremor
intellectual disability, mild
dysmetria
dysdiadochokinesis
more
Head And Neck Teeth:
delayed eruption
hypodontia (variable)
oligodontia (variable)
malpositioning

Endocrine Features:
hypogonadotropic hypogonadism (variable)


Clinical features from OMIM:

614381

Human phenotypes related to Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism:

32 (show all 20)
# Description HPO Frequency HPO Source Accession
1 hypogonadotrophic hypogonadism 32 occasional (7.5%) HP:0000044
2 myopia 32 HP:0000545
3 horizontal nystagmus 32 HP:0000666
4 hypodontia 32 frequent (33%) HP:0000668
5 oligodontia 32 occasional (7.5%) HP:0000677
6 delayed eruption of teeth 32 HP:0000684
7 impaired horizontal smooth pursuit 32 HP:0001151
8 intellectual disability, mild 32 HP:0001256
9 spasticity 32 frequent (33%) HP:0001257
10 dysarthria 32 HP:0001260
11 cerebellar atrophy 32 HP:0001272
12 dysmetria 32 HP:0001310
13 hyperreflexia 32 HP:0001347
14 dysphagia 32 occasional (7.5%) HP:0002015
15 dysdiadochokinesis 32 HP:0002075
16 hypoplasia of the corpus callosum 32 HP:0002079
17 intention tremor 32 HP:0002080
18 leukodystrophy 32 HP:0002415
19 short stature 32 HP:0004322
20 cerebral hypomyelination 32 HP:0006808

UMLS symptoms related to Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism:


cerebellar ataxia, tremor, dysdiadochokinesis

GenomeRNAi Phenotypes related to Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-145 10 CYP2D6
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-179 10 CYP2D6
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-181 10 CYP2D6 POLR3B
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-184 10 CYP2D6
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-212 10 CYP2D6 POLR3B
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 10 POLR3B
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-22 10 POLR3B
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-26 10 CYP2D6
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-40 10 POLR3B
10 Synthetic lethal with c-Myc after tamoxifen stimulation GR00215-A 8.62 LMOD1 CYP2D6

Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia...

Search Clinical Trials , NIH Clinical Center for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism

Genetic Tests for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia...

Genetic tests related to Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism:

# Genetic test Affiliating Genes
1 Hypomyelinating Leukodystrophy 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism 29 POLR3B

Anatomical Context for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia...

MalaCards organs/tissues related to Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism:

41
Brain

Publications for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia...

Variations for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia...

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism:

75
# Symbol AA change Variation ID SNP ID
1 POLR3B p.Thr503Lys VAR_067005 rs267608683
2 POLR3B p.Val523Glu VAR_067006 rs138249161
3 POLR3B p.Arg768His VAR_067008 rs267608687
4 POLR3B p.Asp926Glu VAR_067009 rs267608689
5 POLR3B p.Leu104Phe VAR_072344
6 POLR3B p.Ser268Gly VAR_072345
7 POLR3B p.Arg442Cys VAR_072346
8 POLR3B p.Cys527Arg VAR_072347

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism:

6
(show all 24)
# Gene Variation Type Significance SNP ID Assembly Location
1 POLR3B NM_018082.5(POLR3B): c.1857-2A> C single nucleotide variant Pathogenic rs267608686 GRCh37 Chromosome 12, 106831457: 106831457
2 POLR3B NM_018082.5(POLR3B): c.1857-2A> C single nucleotide variant Pathogenic rs267608686 GRCh38 Chromosome 12, 106437679: 106437679
3 POLR3B NM_018082.5(POLR3B): c.2303G> A (p.Arg768His) single nucleotide variant Pathogenic rs267608687 GRCh37 Chromosome 12, 106850925: 106850925
4 POLR3B NM_018082.5(POLR3B): c.2303G> A (p.Arg768His) single nucleotide variant Pathogenic rs267608687 GRCh38 Chromosome 12, 106457147: 106457147
5 POLR3B NM_018082.5(POLR3B): c.1648C> T (p.Arg550Ter) single nucleotide variant Pathogenic rs267608688 GRCh37 Chromosome 12, 106827517: 106827517
6 POLR3B NM_018082.5(POLR3B): c.1648C> T (p.Arg550Ter) single nucleotide variant Pathogenic rs267608688 GRCh38 Chromosome 12, 106433739: 106433739
7 POLR3B NM_018082.5(POLR3B): c.2778C> G (p.Asp926Glu) single nucleotide variant Pathogenic rs267608689 GRCh37 Chromosome 12, 106889897: 106889897
8 POLR3B NM_018082.5(POLR3B): c.2778C> G (p.Asp926Glu) single nucleotide variant Pathogenic rs267608689 GRCh38 Chromosome 12, 106496119: 106496119
9 POLR3B NM_018082.5(POLR3B): c.1508C> A (p.Thr503Lys) single nucleotide variant Pathogenic rs267608683 GRCh37 Chromosome 12, 106826139: 106826139
10 POLR3B NM_018082.5(POLR3B): c.1508C> A (p.Thr503Lys) single nucleotide variant Pathogenic rs267608683 GRCh38 Chromosome 12, 106432361: 106432361
11 POLR3B NM_018082.5(POLR3B): c.1533delT (p.Ile511Metfs) deletion Pathogenic rs267608684 GRCh37 Chromosome 12, 106826164: 106826164
12 POLR3B NM_018082.5(POLR3B): c.1533delT (p.Ile511Metfs) deletion Pathogenic rs267608684 GRCh38 Chromosome 12, 106432386: 106432386
13 POLR3B NM_018082.5(POLR3B): c.1568T> A (p.Val523Glu) single nucleotide variant Pathogenic rs138249161 GRCh37 Chromosome 12, 106826199: 106826199
14 POLR3B NM_018082.5(POLR3B): c.1568T> A (p.Val523Glu) single nucleotide variant Pathogenic rs138249161 GRCh38 Chromosome 12, 106432421: 106432421
15 POLR3B NM_018082.5(POLR3B): c.2686A> T (p.Lys896Ter) single nucleotide variant Pathogenic rs267608685 GRCh37 Chromosome 12, 106857371: 106857371
16 POLR3B NM_018082.5(POLR3B): c.2686A> T (p.Lys896Ter) single nucleotide variant Pathogenic rs267608685 GRCh38 Chromosome 12, 106463593: 106463593
17 POLR3B NM_018082.5(POLR3B): c.1612_1614delCTT (p.Leu538del) deletion Likely pathogenic rs797045895 GRCh37 Chromosome 12, 106826243: 106826245
18 POLR3B NM_018082.5(POLR3B): c.1612_1614delCTT (p.Leu538del) deletion Likely pathogenic rs797045895 GRCh38 Chromosome 12, 106432465: 106432467
19 POLR3B NM_018082.5(POLR3B): c.3173A> G (p.Tyr1058Cys) single nucleotide variant Likely pathogenic rs751459271 GRCh37 Chromosome 12, 106897933: 106897933
20 POLR3B NM_018082.5(POLR3B): c.3173A> G (p.Tyr1058Cys) single nucleotide variant Likely pathogenic rs751459271 GRCh38 Chromosome 12, 106504155: 106504155
21 POLR3B NM_018082.5(POLR3B): c.1988C> T (p.Thr663Ile) single nucleotide variant no interpretation for the single variant rs755312623 GRCh37 Chromosome 12, 106838273: 106838273
22 POLR3B NM_018082.5(POLR3B): c.1988C> T (p.Thr663Ile) single nucleotide variant no interpretation for the single variant rs755312623 GRCh38 Chromosome 12, 106444495: 106444495
23 POLR3B NM_018082.5(POLR3B): c.2774C> A (p.Pro925Gln) single nucleotide variant Pathogenic rs775141057 GRCh38 Chromosome 12, 106496115: 106496115
24 POLR3B NM_018082.5(POLR3B): c.2774C> A (p.Pro925Gln) single nucleotide variant Pathogenic rs775141057 GRCh37 Chromosome 12, 106889893: 106889893

Expression for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia...

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism.

Pathways for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia...

GO Terms for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia...

Sources for Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....