PCH1B
MCID: PNT018
MIFTS: 43

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 56 29 13 6 71
Pontocerebellar Hypoplasia Type 1b 12 15
Pch1b 56 73
Hypoplasia, Pontocerebellar, Type 1b 39
Pontocerebellar Hypoplasia 1b 73

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset at birth
early death may occur


HPO:

31
pontocerebellar hypoplasia, type 1b:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity congenital onset


Classifications:



Summaries for Pontocerebellar Hypoplasia, Type 1b

OMIM : 56 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 Gene Expression and Metabolism of proteins. 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 : 73 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:

31 (show all 25)
# Description HPO Frequency HPO Source Accession
1 seizures 31 occasional (7.5%) HP:0001250
2 retinal dystrophy 31 occasional (7.5%) HP:0000556
3 nystagmus 31 HP:0000639
4 spasticity 31 HP:0001257
5 hyperreflexia 31 HP:0001347
6 respiratory insufficiency 31 HP:0002093
7 global developmental delay 31 HP:0001263
8 feeding difficulties 31 HP:0011968
9 flexion contracture 31 HP:0001371
10 skeletal muscle atrophy 31 HP:0003202
11 generalized hypotonia 31 HP:0001290
12 tongue fasciculations 31 HP:0001308
13 strabismus 31 HP:0000486
14 absent speech 31 HP:0001344
15 growth delay 31 HP:0001510
16 abnormality of the foot 31 HP:0001760
17 hip dislocation 31 HP:0002827
18 cerebellar atrophy 31 HP:0001272
19 oculomotor apraxia 31 HP:0000657
20 poor head control 31 HP:0002421
21 cerebral atrophy 31 HP:0002059
22 muscular hypotonia of the trunk 31 HP:0008936
23 progressive microcephaly 31 HP:0000253
24 tongue atrophy 31 HP:0012473
25 cerebellar cyst 31 HP:0002350

Symptoms via clinical synopsis from OMIM:

56
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

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

26 (show all 18)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-108 9.9 EXOSC8
2 Increased shRNA abundance (Z-score > 2) GR00366-A-126 9.9 EXOSC9
3 Increased shRNA abundance (Z-score > 2) GR00366-A-131 9.9 EXOSC9
4 Increased shRNA abundance (Z-score > 2) GR00366-A-146 9.9 EXOSC8
5 Increased shRNA abundance (Z-score > 2) GR00366-A-157 9.9 EXOSC8 EXOSC9
6 Increased shRNA abundance (Z-score > 2) GR00366-A-159 9.9 EXOSC8
7 Increased shRNA abundance (Z-score > 2) GR00366-A-166 9.9 EXOSC8
8 Increased shRNA abundance (Z-score > 2) GR00366-A-173 9.9 EXOSC8 EXOSC9 SGSM1
9 Increased shRNA abundance (Z-score > 2) GR00366-A-177 9.9 EXOSC9
10 Increased shRNA abundance (Z-score > 2) GR00366-A-180 9.9 SGSM1
11 Increased shRNA abundance (Z-score > 2) GR00366-A-201 9.9 EXOSC8
12 Increased shRNA abundance (Z-score > 2) GR00366-A-46 9.9 SGSM1
13 Increased shRNA abundance (Z-score > 2) GR00366-A-60 9.9 EXOSC8
14 Increased shRNA abundance (Z-score > 2) GR00366-A-73 9.9 EXOSC9
15 Increased shRNA abundance (Z-score > 2) GR00366-A-76 9.9 SGSM1
16 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.9 EXOSC9
17 Increased shRNA abundance (Z-score > 2) GR00366-A-9 9.9 EXOSC9
18 Increased shRNA abundance (Z-score > 2) GR00366-A-99 9.9 EXOSC9

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

Anatomical Context for Pontocerebellar Hypoplasia, Type 1b

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

40
Tongue, Spinal Cord, Skeletal Muscle, Pons, Cerebellum

Publications for Pontocerebellar Hypoplasia, Type 1b

Articles related to Pontocerebellar Hypoplasia, Type 1b:

(show all 19)
# Title Authors PMID Year
1
Novel EXOSC3 mutation causes complicated hereditary spastic paraplegia. 56 6
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. 6 56
23883322 2013
3
Exome sequencing in a family with intellectual disability, early onset spasticity, and cerebellar atrophy detects a novel mutation in EXOSC3. 6 56
23975261 2013
4
Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration. 56 6
22544365 2012
5
EXOSC3-Related Pontocerebellar Hypoplasia 6
25144110 2014
6
EXOSC3 mutations in pontocerebellar hypoplasia type 1: novel mutations and genotype-phenotype correlations. 56
24524299 2014
7
EXOSC3 mutations in isolated cerebellar hypoplasia and spinal anterior horn involvement. 56
23564332 2013
8
Pontocerebellar hypoplasia type 1: clinical spectrum and relevance of EXOSC3 mutations. 56
23284067 2013
9
Pontocerebellar hypoplasia type 1: new leads for an earlier diagnosis. 56
12731647 2003
10
Extended phenotype of pontocerebellar hypoplasia with infantile spinal muscular atrophy. 56
12548734 2003
11
Anterior horn cell disease and olivopontocerebellar hypoplasia. 56
11020648 2000
12
The RNA Exosome and Human Disease. 61
31768969 2020
13
Infantile onset progressive cerebellar atrophy and anterior horn cell Degeneration-A novel phenotype associated with mutations in the PLA2G6 gene. 61
31689548 2019
14
Pontocerebellar hypoplasia with rhombencephalosynapsis and microlissencephaly expands the spectrum of PCH type 1B. 61
31770597 2019
15
Novel EXOSC3 pathogenic variant results in a mild course of neurologic disease with cerebellum involvement. 61
30986545 2019
16
A Chemical Biology Approach to Model Pontocerebellar Hypoplasia Type 1B (PCH1B). 61
30141626 2018
17
The RNA exosome and RNA exosome-linked disease. 61
29093021 2018
18
Recessive mutation in EXOSC3 associates with mitochondrial dysfunction and pontocerebellar hypoplasia. 61
28687512 2017
19
Insight into the RNA Exosome Complex Through Modeling Pontocerebellar Hypoplasia Type 1b Disease Mutations in Yeast. 61
27777260 2017

Variations for Pontocerebellar Hypoplasia, Type 1b

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

6 (show all 19) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 EXOSC3 NM_016042.4(EXOSC3):c.415G>C (p.Ala139Pro)SNV Pathogenic 31689 rs387907195 9:37783970-37783970 9:37783973-37783973
2 EXOSC3 NM_016042.4(EXOSC3):c.294_303del (p.Val99fs)deletion Pathogenic 31690 rs672601331 9:37784739-37784748 9:37784742-37784751
3 EXOSC3 NM_016042.4(EXOSC3):c.92G>C (p.Gly31Ala)SNV Pathogenic 31691 rs387907196 9:37784950-37784950 9:37784953-37784953
4 EXOSC3 NM_016042.4(EXOSC3):c.712T>C (p.Trp238Arg)SNV Pathogenic 31692 rs672601332 9:37780792-37780792 9:37780795-37780795
5 EXOSC3 NM_016042.4(EXOSC3):c.112del (p.Glu38fs)deletion Pathogenic 129023 rs587780333 9:37784930-37784930 9:37784933-37784933
6 EXOSC3 NM_016042.4(EXOSC3):c.571G>T (p.Gly191Cys)SNV Pathogenic 183048 rs730882145 9:37782038-37782038 9:37782041-37782041
7 EXOSC3 NM_016042.4(EXOSC3):c.155del (p.Pro52fs)deletion Pathogenic 280004 rs886041316 9:37784887-37784887 9:37784890-37784890
8 EXOSC3 NM_016042.4(EXOSC3):c.395A>C (p.Asp132Ala)SNV Pathogenic/Likely pathogenic 31688 rs141138948 9:37783990-37783990 9:37783993-37783993
9 VRK1 NM_003384.3(VRK1):c.156_160+3deldeletion Likely pathogenic 624564 rs1566696845 14:97299964-97299971 14:96833627-96833634
10 EXOSC3 NM_016042.4(EXOSC3):c.238G>T (p.Val80Phe)SNV Likely pathogenic 129024 rs374550999 9:37784804-37784804 9:37784807-37784807
11 EXOSC3 NM_016042.4(EXOSC3):c.572G>A (p.Gly191Asp)SNV Conflicting interpretations of pathogenicity 210965 rs797045567 9:37782037-37782037 9:37782040-37782040
12 EXOSC3 NM_016042.4(EXOSC3):c.475-12A>GSNV Conflicting interpretations of pathogenicity 488793 rs370087266 9:37782146-37782146 9:37782149-37782149
13 EXOSC3 NM_016042.4(EXOSC3):c.782C>T (p.Thr261Met)SNV Uncertain significance 571172 9:37780722-37780722 9:37780725-37780725
14 EXOSC3 NM_016042.4(EXOSC3):c.785C>T (p.Ser262Leu)SNV Uncertain significance 661315 9:37780719-37780719 9:37780722-37780722
15 EXOSC3 NM_016042.4(EXOSC3):c.52_53delinsTC (p.Arg18Ser)indel Uncertain significance 650346 9:37784989-37784990 9:37784992-37784993
16 EXOSC3 NM_016042.4(EXOSC3):c.328G>A (p.Val110Ile)SNV Uncertain significance 210964 rs138169215 9:37784057-37784057 9:37784060-37784060
17 EXOSC3 NM_016042.4(EXOSC3):c.588T>C (p.Asp196=)SNV Likely benign 386440 rs147568068 9:37782021-37782021 9:37782024-37782024
18 EXOSC3 NM_016042.4(EXOSC3):c.540T>C (p.Cys180=)SNV Benign/Likely benign 384297 rs62640003 9:37782069-37782069 9:37782072-37782072
19 EXOSC3 NM_016042.4(EXOSC3):c.498G>A (p.Gln166=)SNV Benign 129025 rs7158 9:37782111-37782111 9:37782114-37782114

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

73
# 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

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 cytoplasm GO:0005737 9.95 VRK1 SGSM1 EXOSC9 EXOSC8 EXOSC3 EXOSC2
2 cytosol GO:0005829 9.87 VRK1 SGSM1 EXOSC9 EXOSC8 EXOSC3 EXOSC2
3 nucleoplasm GO:0005654 9.85 VRK1 EXOSC9 EXOSC8 EXOSC3 EXOSC2 DIS3
4 nucleolus GO:0005730 9.73 VRK1 EXOSC9 EXOSC8 EXOSC3 EXOSC2 DIS3
5 exosome (RNase complex) GO:0000178 9.55 EXOSC9 EXOSC8 EXOSC3 EXOSC2 DIS3
6 nuclear exosome (RNase complex) GO:0000176 9.35 EXOSC9 EXOSC8 EXOSC3 EXOSC2 DIS3
7 cytoplasmic exosome (RNase complex) GO:0000177 9.02 EXOSC9 EXOSC8 EXOSC3 EXOSC2 DIS3

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

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 rRNA processing GO:0006364 9.85 EXOSC9 EXOSC8 EXOSC3 EXOSC2 DIS3
2 regulation of mRNA stability GO:0043488 9.8 EXOSC9 EXOSC8 EXOSC3 EXOSC2 DIS3
3 nuclear-transcribed mRNA catabolic process, exonucleolytic, 3'-5' GO:0034427 9.67 EXOSC9 EXOSC8 EXOSC3 EXOSC2
4 rRNA catabolic process GO:0016075 9.65 EXOSC9 EXOSC8 DIS3
5 U4 snRNA 3'-end processing GO:0034475 9.62 EXOSC9 EXOSC8 EXOSC3 EXOSC2
6 CUT catabolic process GO:0071034 9.61 EXOSC3 EXOSC2 DIS3
7 RNA processing GO:0006396 9.58 EXOSC9 EXOSC8
8 positive regulation of cell growth GO:0030307 9.57 EXOSC9 EXOSC2
9 nuclear mRNA surveillance GO:0071028 9.56 EXOSC9 EXOSC8
10 exonucleolytic trimming to generate mature 3'-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) GO:0000467 9.56 EXOSC9 EXOSC8 EXOSC3 EXOSC2
11 polyadenylation-dependent snoRNA 3'-end processing GO:0071051 9.55 EXOSC3 EXOSC2
12 nuclear polyadenylation-dependent mRNA catabolic process GO:0071042 9.54 EXOSC9 EXOSC8
13 U5 snRNA 3'-end processing GO:0034476 9.52 EXOSC9 EXOSC8
14 U1 snRNA 3'-end processing GO:0034473 9.51 EXOSC9 EXOSC8
15 nuclear retention of pre-mRNA with aberrant 3'-ends at the site of transcription GO:0071049 9.49 EXOSC3 EXOSC2
16 nuclear polyadenylation-dependent tRNA catabolic process GO:0071038 9.46 EXOSC9 EXOSC8 EXOSC3 EXOSC2
17 nuclear polyadenylation-dependent rRNA catabolic process GO:0071035 9.26 EXOSC9 EXOSC8 EXOSC3 EXOSC2
18 exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay GO:0043928 9.02 EXOSC9 EXOSC8 EXOSC3 EXOSC2 DIS3

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

# Name GO ID Score Top Affiliating Genes
1 RNA binding GO:0003723 9.55 EXOSC9 EXOSC8 EXOSC3 EXOSC2 DIS3
2 mRNA 3'-UTR AU-rich region binding GO:0035925 9.26 EXOSC9 EXOSC8
3 3'-5'-exoribonuclease activity GO:0000175 9.26 EXOSC9 EXOSC3 EXOSC2 DIS3
4 exoribonuclease activity GO:0004532 8.92 EXOSC9 EXOSC8 EXOSC3 EXOSC2

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 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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