HLD8
MCID: LKD018
MIFTS: 31

Leukodystrophy, Hypomyelinating, 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism (HLD8)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare 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 58 76 13 74
Hld8 58 12 76
Hypomyelinating Leukodystrophy 8, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism 30 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 41

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

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


HPO:

33
leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism:
Inheritance autosomal recessive inheritance


Classifications:



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

OMIM : 58 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 polr3-related leukodystrophy, and has symptoms including tremor, dysdiadochokinesis and cerebellar ataxia. 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 eye, and related phenotypes are spasticity and hypodontia

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 : 76 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 in the Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism family:

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

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 polr3-related leukodystrophy 11.8
3 leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism 11.2
4 leukodystrophy, hypomyelinating, 13 9.5 CYP2D6 LMOD1

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

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

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

Symptoms via clinical synopsis from OMIM:

58
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

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


tremor, dysdiadochokinesis, cerebellar ataxia

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

27
# 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 CYP2D6 LMOD1

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 30 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:

42
Brain, Eye

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

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

# Title Authors Year
1
Clinical spectrum of 4H leukodystrophy caused by POLR3A and POLR3B mutations. ( 25339210 )
2014
2
Mutations in POLR3A and POLR3B encoding RNA Polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy. ( 22036171 )
2011
3
Recessive mutations in POLR3B, encoding the second largest subunit of Pol III, cause a rare hypomyelinating leukodystrophy. ( 22036172 )
2011
4
Diffuse cerebral hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum. ( 18851904 )
2009

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:

76
# 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 rs144221268
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 28)
# 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.1244T> C (p.Met415Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs199504211 GRCh37 Chromosome 12, 106821117: 106821117
22 POLR3B NM_018082.5(POLR3B): c.1244T> C (p.Met415Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs199504211 GRCh38 Chromosome 12, 106427339: 106427339
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
25 POLR3B NM_018082.5(POLR3B): c.1263+2T> C single nucleotide variant Likely pathogenic rs774526181 GRCh37 Chromosome 12, 106821138: 106821138
26 POLR3B NM_018082.5(POLR3B): c.1263+2T> C single nucleotide variant Likely pathogenic rs774526181 GRCh38 Chromosome 12, 106427360: 106427360
27 POLR3B NM_018082.6(POLR3B): c.2570+1G> A single nucleotide variant Pathogenic GRCh38 Chromosome 12, 106459369: 106459369
28 POLR3B NM_018082.6(POLR3B): c.2570+1G> A single nucleotide variant Pathogenic GRCh37 Chromosome 12, 106853147: 106853147

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...

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