PCH1B
MCID: PNT018
MIFTS: 39

Pontocerebellar Hypoplasia, Type 1b (PCH1B)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Pontocerebellar Hypoplasia, Type 1b

MalaCards integrated aliases for Pontocerebellar Hypoplasia, Type 1b:

Name: Pontocerebellar Hypoplasia, Type 1b 57 29 13 6 72
Pontocerebellar Hypoplasia Type 1b 12 15
Pch1b 57 74
Hypoplasia, Pontocerebellar, Type 1b 40
Pontocerebellar Hypoplasia 1b 74

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset at birth
early death may occur


HPO:

32
pontocerebellar hypoplasia, type 1b:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity congenital onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0060266
MeSH 44 D002526
UMLS 72 C3553449

Summaries for Pontocerebellar Hypoplasia, Type 1b

OMIM : 57 Pontocerebellar hypoplasia type 1B is a severe autosomal recessive neurologic disorder characterized by a combination of cerebellar and spinal motor neuron degeneration beginning at birth. There is diffuse muscle weakness, progressive microcephaly, global developmental delay, and brainstem involvement (summary by Wan et al., 2012). PCH1B can be divided into mild, moderate, and severe subgroups that vary in age at onset, progression, clinical and neuroradiologic severity, and survival (summary by Halevy et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1A (607596). (614678)

MalaCards based summary : Pontocerebellar Hypoplasia, Type 1b, also known as pontocerebellar hypoplasia type 1b, is related to pontocerebellar hypoplasia and exosc3-related pontocerebellar hypoplasia, and has symptoms including muscle weakness and muscle spasticity. An important gene associated with Pontocerebellar Hypoplasia, Type 1b is EXOSC3 (Exosome Component 3), and among its related pathways/superpathways are Unfolded Protein Response (UPR) and Deadenylation-dependent mRNA decay. Affiliated tissues include tongue, spinal cord and skeletal muscle, and related phenotypes are seizures and retinal dystrophy

Disease Ontology : 12 A severe pontocerebellar hypoplasia that is characterized by hypotonia, progressive microcephaly and developmental delay, has material basis in autosomal recessive inheritance of mutation in the EXOSC3 gene.

UniProtKB/Swiss-Prot : 74 Pontocerebellar hypoplasia 1B: A severe autosomal recessive neurologic disorder characterized by a combination of cerebellar and spinal motor neuron degeneration beginning at birth. There is diffuse muscle weakness, progressive microcephaly, global developmental delay, and brainstem involvement.

Related Diseases for Pontocerebellar Hypoplasia, Type 1b

Graphical network of the top 20 diseases related to Pontocerebellar Hypoplasia, Type 1b:



Diseases related to Pontocerebellar Hypoplasia, Type 1b

Symptoms & Phenotypes for Pontocerebellar Hypoplasia, Type 1b

Human phenotypes related to Pontocerebellar Hypoplasia, Type 1b:

32 (show all 25)
# Description HPO Frequency HPO Source Accession
1 seizures 32 occasional (7.5%) HP:0001250
2 retinal dystrophy 32 occasional (7.5%) HP:0000556
3 nystagmus 32 HP:0000639
4 spasticity 32 HP:0001257
5 hyperreflexia 32 HP:0001347
6 respiratory insufficiency 32 HP:0002093
7 global developmental delay 32 HP:0001263
8 flexion contracture 32 HP:0001371
9 skeletal muscle atrophy 32 HP:0003202
10 generalized hypotonia 32 HP:0001290
11 feeding difficulties 32 HP:0011968
12 tongue fasciculations 32 HP:0001308
13 strabismus 32 HP:0000486
14 absent speech 32 HP:0001344
15 growth delay 32 HP:0001510
16 abnormality of the foot 32 HP:0001760
17 hip dislocation 32 HP:0002827
18 cerebellar atrophy 32 HP:0001272
19 oculomotor apraxia 32 HP:0000657
20 poor head control 32 HP:0002421
21 cerebral atrophy 32 HP:0002059
22 muscular hypotonia of the trunk 32 HP:0008936
23 progressive microcephaly 32 HP:0000253
24 tongue atrophy 32 HP:0012473
25 cerebellar cyst 32 HP:0002350

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus
strabismus
oculomotor apraxia
poor visual attention
retinal dystrophy (1 family)

Muscle Soft Tissue:
muscle weakness
hypotonia
muscle atrophy
emg shows neurogenic changes

Head And Neck Mouth:
tongue fasciculations
tongue atrophy

Head And Neck Head:
poor head control
microcephaly, postnatal, progressive (-2 to -3.5 sd)

Skeletal:
joint contractures

Neurologic Peripheral Nervous System:
axonal motor neuropathy

Neurologic Central Nervous System:
spasticity
hyperreflexia
cerebellar atrophy
cerebral atrophy
seizures (in some patients)
more
Respiratory:
respiratory insufficiency

Skeletal Pelvis:
hip dislocation

Abdomen Gastrointestinal:
poor feeding

Skeletal Feet:
foot deformities

Growth Other:
poor growth, postnatal

Clinical features from OMIM:

614678

UMLS symptoms related to Pontocerebellar Hypoplasia, Type 1b:


muscle weakness, muscle spasticity

Drugs & Therapeutics for Pontocerebellar Hypoplasia, Type 1b

Search Clinical Trials , NIH Clinical Center for Pontocerebellar Hypoplasia, Type 1b

Genetic Tests for Pontocerebellar Hypoplasia, Type 1b

Genetic tests related to Pontocerebellar Hypoplasia, Type 1b:

# Genetic test Affiliating Genes
1 Pontocerebellar Hypoplasia, Type 1b 29 EXOSC3

Anatomical Context for Pontocerebellar Hypoplasia, Type 1b

MalaCards organs/tissues related to Pontocerebellar Hypoplasia, Type 1b:

41
Tongue, Spinal Cord, Skeletal Muscle, Pons, Cerebellum

Publications for Pontocerebellar Hypoplasia, Type 1b

Articles related to Pontocerebellar Hypoplasia, Type 1b:

(show all 16)
# Title Authors PMID Year
1
Novel EXOSC3 mutation causes complicated hereditary spastic paraplegia. 8 71
25149867 2014
2
Homozygous EXOSC3 mutation c.92G→C, p.G31A is a founder mutation causing severe pontocerebellar hypoplasia type 1 among the Czech Roma. 8 71
23883322 2013
3
Exome sequencing in a family with intellectual disability, early onset spasticity, and cerebellar atrophy detects a novel mutation in EXOSC3. 8 71
23975261 2013
4
Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration. 8 71
22544365 2012
5
EXOSC3-Related Pontocerebellar Hypoplasia 71
25144110 2014
6
EXOSC3 mutations in pontocerebellar hypoplasia type 1: novel mutations and genotype-phenotype correlations. 8
24524299 2014
7
EXOSC3 mutations in isolated cerebellar hypoplasia and spinal anterior horn involvement. 8
23564332 2013
8
Pontocerebellar hypoplasia type 1: clinical spectrum and relevance of EXOSC3 mutations. 8
23284067 2013
9
Pontocerebellar hypoplasia type 1: new leads for an earlier diagnosis. 8
12731647 2003
10
Extended phenotype of pontocerebellar hypoplasia with infantile spinal muscular atrophy. 8
12548734 2003
11
Anterior horn cell disease and olivopontocerebellar hypoplasia. 8
11020648 2000
12
Novel EXOSC3 pathogenic variant results in a mild course of neurologic disease with cerebellum involvement. 38
30986545 2019
13
A Chemical Biology Approach to Model Pontocerebellar Hypoplasia Type 1B (PCH1B). 38
30141626 2018
14
The RNA exosome and RNA exosome-linked disease. 38
29093021 2018
15
Recessive mutation in EXOSC3 associates with mitochondrial dysfunction and pontocerebellar hypoplasia. 38
28687512 2017
16
Insight into the RNA Exosome Complex Through Modeling Pontocerebellar Hypoplasia Type 1b Disease Mutations in Yeast. 38
27777260 2017

Variations for Pontocerebellar Hypoplasia, Type 1b

ClinVar genetic disease variations for Pontocerebellar Hypoplasia, Type 1b:

6 (show all 19)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 EXOSC3 NM_016042.4(EXOSC3): c.415G> C (p.Ala139Pro) single nucleotide variant Pathogenic rs387907195 9:37783970-37783970 9:37783973-37783973
2 EXOSC3 NM_016042.4(EXOSC3): c.294_303del (p.Val99fs) deletion Pathogenic rs672601331 9:37784739-37784748 9:37784742-37784751
3 EXOSC3 NM_016042.4(EXOSC3): c.92G> C (p.Gly31Ala) single nucleotide variant Pathogenic rs387907196 9:37784950-37784950 9:37784953-37784953
4 EXOSC3 NM_016042.4(EXOSC3): c.712T> C (p.Trp238Arg) single nucleotide variant Pathogenic rs672601332 9:37780792-37780792 9:37780795-37780795
5 EXOSC3 NM_016042.4(EXOSC3): c.112del (p.Glu38fs) deletion Pathogenic rs587780333 9:37784930-37784930 9:37784933-37784933
6 EXOSC3 NM_016042.4(EXOSC3): c.571G> T (p.Gly191Cys) single nucleotide variant Pathogenic rs730882145 9:37782038-37782038 9:37782041-37782041
7 EXOSC3 NM_016042.4(EXOSC3): c.155del (p.Pro52fs) deletion Pathogenic rs886041316 9:37784887-37784887 9:37784890-37784890
8 EXOSC3 NM_016042.4(EXOSC3): c.395A> C (p.Asp132Ala) single nucleotide variant Pathogenic/Likely pathogenic rs141138948 9:37783990-37783990 9:37783993-37783993
9 EXOSC3 NM_016042.4(EXOSC3): c.238G> T (p.Val80Phe) single nucleotide variant Likely pathogenic rs374550999 9:37784804-37784804 9:37784807-37784807
10 VRK1 NM_003384.3(VRK1): c.156_160+3del deletion Likely pathogenic 14:97299964-97299971 14:96833627-96833634
11 EXOSC3 NM_016042.4(EXOSC3): c.572G> A (p.Gly191Asp) single nucleotide variant Conflicting interpretations of pathogenicity rs797045567 9:37782037-37782037 9:37782040-37782040
12 EXOSC3 NM_016042.4(EXOSC3): c.475-12A> G single nucleotide variant Conflicting interpretations of pathogenicity rs370087266 9:37782146-37782146 9:37782149-37782149
13 EXOSC3 NM_016042.4(EXOSC3): c.328G> A (p.Val110Ile) single nucleotide variant Uncertain significance rs138169215 9:37784057-37784057 9:37784060-37784060
14 EXOSC3 NM_016042.4(EXOSC3): c.782C> T (p.Thr261Met) single nucleotide variant Uncertain significance 9:37780722-37780722 9:37780725-37780725
15 EXOSC3 NM_016042.4(EXOSC3): c.785C> T (p.Ser262Leu) single nucleotide variant Uncertain significance 9:37780719-37780719 9:37780722-37780722
16 EXOSC3 NM_016042.4(EXOSC3): c.52_53delinsTC (p.Arg18Ser) indel Uncertain significance 9:37784989-37784990 9:37784992-37784993
17 EXOSC3 NM_016042.4(EXOSC3): c.588T> C (p.Asp196=) single nucleotide variant Likely benign rs147568068 9:37782021-37782021 9:37782024-37782024
18 EXOSC3 NM_016042.4(EXOSC3): c.540T> C (p.Cys180=) single nucleotide variant Benign/Likely benign rs62640003 9:37782069-37782069 9:37782072-37782072
19 EXOSC3 NM_016042.4(EXOSC3): c.498G> A (p.Gln166=) single nucleotide variant Benign rs7158 9:37782111-37782111 9:37782114-37782114

UniProtKB/Swiss-Prot genetic disease variations for Pontocerebellar Hypoplasia, Type 1b:

74
# Symbol AA change Variation ID SNP ID
1 EXOSC3 p.Gly31Ala VAR_068505 rs387907196
2 EXOSC3 p.Asp132Ala VAR_068506 rs141138948
3 EXOSC3 p.Ala139Pro VAR_068507 rs387907195
4 EXOSC3 p.Trp238Arg VAR_068508 rs672601332

Expression for Pontocerebellar Hypoplasia, Type 1b

Search GEO for disease gene expression data for Pontocerebellar Hypoplasia, Type 1b.

Pathways for Pontocerebellar Hypoplasia, Type 1b

Pathways related to Pontocerebellar Hypoplasia, Type 1b according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.52 EXOSC8 EXOSC3
2
Show member pathways
11.24 EXOSC8 EXOSC3
3
Show member pathways
10.38 EXOSC8 EXOSC3

GO Terms for Pontocerebellar Hypoplasia, Type 1b

Cellular components related to Pontocerebellar Hypoplasia, Type 1b according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleolus GO:0005730 9.43 VRK1 EXOSC8 EXOSC3
2 exosome (RNase complex) GO:0000178 9.16 EXOSC8 EXOSC3
3 nuclear exosome (RNase complex) GO:0000176 8.96 EXOSC8 EXOSC3
4 cytoplasmic exosome (RNase complex) GO:0000177 8.62 EXOSC8 EXOSC3

Biological processes related to Pontocerebellar Hypoplasia, Type 1b according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 rRNA processing GO:0006364 9.43 EXOSC8 EXOSC3
2 regulation of mRNA stability GO:0043488 9.4 EXOSC8 EXOSC3
3 exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay GO:0043928 9.37 EXOSC8 EXOSC3
4 nuclear-transcribed mRNA catabolic process, exonucleolytic, 3'-5' GO:0034427 9.32 EXOSC8 EXOSC3
5 U4 snRNA 3'-end processing GO:0034475 9.26 EXOSC8 EXOSC3
6 nuclear polyadenylation-dependent rRNA catabolic process GO:0071035 9.16 EXOSC8 EXOSC3
7 nuclear polyadenylation-dependent tRNA catabolic process GO:0071038 8.96 EXOSC8 EXOSC3
8 exonucleolytic trimming to generate mature 3'-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) GO:0000467 8.62 EXOSC8 EXOSC3

Molecular functions related to Pontocerebellar Hypoplasia, Type 1b according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 exoribonuclease activity GO:0004532 8.62 EXOSC8 EXOSC3

Sources for Pontocerebellar Hypoplasia, Type 1b

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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