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 58 30 13 6 74
Pontocerebellar Hypoplasia Type 1b 12 15
Pch1b 58 76
Hypoplasia, Pontocerebellar, Type 1b 41
Pontocerebellar Hypoplasia 1b 76

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset at birth
early death may occur


HPO:

33
pontocerebellar hypoplasia, type 1b:
Onset and clinical course variable expressivity congenital onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Pontocerebellar Hypoplasia, Type 1b

OMIM : 58 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 : 76 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

Symptoms & Phenotypes for Pontocerebellar Hypoplasia, Type 1b

Human phenotypes related to Pontocerebellar Hypoplasia, Type 1b:

33 (show all 25)
# Description HPO Frequency HPO Source Accession
1 seizures 33 occasional (7.5%) HP:0001250
2 retinal dystrophy 33 occasional (7.5%) HP:0000556
3 nystagmus 33 HP:0000639
4 spasticity 33 HP:0001257
5 hyperreflexia 33 HP:0001347
6 respiratory insufficiency 33 HP:0002093
7 global developmental delay 33 HP:0001263
8 flexion contracture 33 HP:0001371
9 skeletal muscle atrophy 33 HP:0003202
10 feeding difficulties 33 HP:0011968
11 strabismus 33 HP:0000486
12 absent speech 33 HP:0001344
13 growth delay 33 HP:0001510
14 abnormality of the foot 33 HP:0001760
15 hip dislocation 33 HP:0002827
16 cerebellar atrophy 33 HP:0001272
17 generalized hypotonia 33 HP:0001290
18 oculomotor apraxia 33 HP:0000657
19 cerebral atrophy 33 HP:0002059
20 poor head control 33 HP:0002421
21 muscular hypotonia of the trunk 33 HP:0008936
22 progressive microcephaly 33 HP:0000253
23 tongue fasciculations 33 HP:0001308
24 tongue atrophy 33 HP:0012473
25 cerebellar cyst 33 HP:0002350

Symptoms via clinical synopsis from OMIM:

58
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

Skeletal Pelvis:
hip dislocation

Head And Neck Mouth:
tongue fasciculations
tongue atrophy

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

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

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 30 EXOSC3

Anatomical Context for Pontocerebellar Hypoplasia, Type 1b

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

42
Tongue, Spinal Cord, Skeletal Muscle, Pons, Eye

Publications for Pontocerebellar Hypoplasia, Type 1b

Articles related to Pontocerebellar Hypoplasia, Type 1b:

# Title Authors Year
1
A Chemical Biology Approach to Model Pontocerebellar Hypoplasia Type 1B (PCH1B). ( 30141626 )
2018
2
Insight into the RNA Exosome Complex Through Modeling Pontocerebellar Hypoplasia Type 1b Disease Mutations in Yeast. ( 27777260 )
2017
3
Novel EXOSC3 mutation causes complicated hereditary spastic paraplegia. ( 25149867 )
2014
4
Homozygous EXOSC3 mutation c.92G→C, p.G31A is a founder mutation causing severe pontocerebellar hypoplasia type 1 among the Czech Roma. ( 23883322 )
2013
5
Exome sequencing in a family with intellectual disability, early onset spasticity, and cerebellar atrophy detects a novel mutation in EXOSC3. ( 23975261 )
2013
6
Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration. ( 22544365 )
2012

Variations for Pontocerebellar Hypoplasia, Type 1b

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

76
# 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

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

6 (show all 34)
# Gene Variation Type Significance SNP ID Assembly Location
1 EXOSC3 NM_016042.4(EXOSC3): c.395A> C (p.Asp132Ala) single nucleotide variant Pathogenic/Likely pathogenic rs141138948 GRCh37 Chromosome 9, 37783990: 37783990
2 EXOSC3 NM_016042.4(EXOSC3): c.395A> C (p.Asp132Ala) single nucleotide variant Pathogenic/Likely pathogenic rs141138948 GRCh38 Chromosome 9, 37783993: 37783993
3 EXOSC3 NM_016042.3(EXOSC3): c.415G> C (p.Ala139Pro) single nucleotide variant Pathogenic rs387907195 GRCh37 Chromosome 9, 37783970: 37783970
4 EXOSC3 NM_016042.3(EXOSC3): c.415G> C (p.Ala139Pro) single nucleotide variant Pathogenic rs387907195 GRCh38 Chromosome 9, 37783973: 37783973
5 EXOSC3 NM_016042.3(EXOSC3): c.294_303delTGTTTACTGG (p.Val99Trpfs) deletion Pathogenic rs672601331 GRCh37 Chromosome 9, 37784739: 37784748
6 EXOSC3 NM_016042.3(EXOSC3): c.294_303delTGTTTACTGG (p.Val99Trpfs) deletion Pathogenic rs672601331 GRCh38 Chromosome 9, 37784742: 37784751
7 EXOSC3 NM_016042.3(EXOSC3): c.92G> C (p.Gly31Ala) single nucleotide variant Pathogenic rs387907196 GRCh37 Chromosome 9, 37784950: 37784950
8 EXOSC3 NM_016042.3(EXOSC3): c.92G> C (p.Gly31Ala) single nucleotide variant Pathogenic rs387907196 GRCh38 Chromosome 9, 37784953: 37784953
9 EXOSC3 NM_016042.3(EXOSC3): c.712T> C (p.Trp238Arg) single nucleotide variant Pathogenic rs672601332 GRCh38 Chromosome 9, 37780795: 37780795
10 EXOSC3 NM_016042.3(EXOSC3): c.712T> C (p.Trp238Arg) single nucleotide variant Pathogenic rs672601332 GRCh37 Chromosome 9, 37780792: 37780792
11 EXOSC3 NM_016042.3(EXOSC3): c.112delG (p.Glu38Asnfs) deletion Pathogenic rs587780333 GRCh37 Chromosome 9, 37784930: 37784930
12 EXOSC3 NM_016042.3(EXOSC3): c.112delG (p.Glu38Asnfs) deletion Pathogenic rs587780333 GRCh38 Chromosome 9, 37784933: 37784933
13 EXOSC3 NM_016042.3(EXOSC3): c.238G> T (p.Val80Phe) single nucleotide variant Likely pathogenic rs374550999 GRCh37 Chromosome 9, 37784804: 37784804
14 EXOSC3 NM_016042.3(EXOSC3): c.238G> T (p.Val80Phe) single nucleotide variant Likely pathogenic rs374550999 GRCh38 Chromosome 9, 37784807: 37784807
15 EXOSC3 NM_016042.3(EXOSC3): c.498G> A (p.Gln166=) single nucleotide variant Benign rs7158 GRCh37 Chromosome 9, 37782111: 37782111
16 EXOSC3 NM_016042.3(EXOSC3): c.498G> A (p.Gln166=) single nucleotide variant Benign rs7158 GRCh38 Chromosome 9, 37782114: 37782114
17 EXOSC3 NM_016042.3(EXOSC3): c.571G> T (p.Gly191Cys) single nucleotide variant Pathogenic rs730882145 GRCh37 Chromosome 9, 37782038: 37782038
18 EXOSC3 NM_016042.3(EXOSC3): c.571G> T (p.Gly191Cys) single nucleotide variant Pathogenic rs730882145 GRCh38 Chromosome 9, 37782041: 37782041
19 EXOSC3 NM_016042.3(EXOSC3): c.572G> A (p.Gly191Asp) single nucleotide variant Conflicting interpretations of pathogenicity rs797045567 GRCh38 Chromosome 9, 37782040: 37782040
20 EXOSC3 NM_016042.3(EXOSC3): c.572G> A (p.Gly191Asp) single nucleotide variant Conflicting interpretations of pathogenicity rs797045567 GRCh37 Chromosome 9, 37782037: 37782037
21 EXOSC3 NM_016042.3(EXOSC3): c.328G> A (p.Val110Ile) single nucleotide variant Uncertain significance rs138169215 GRCh37 Chromosome 9, 37784057: 37784057
22 EXOSC3 NM_016042.3(EXOSC3): c.328G> A (p.Val110Ile) single nucleotide variant Uncertain significance rs138169215 GRCh38 Chromosome 9, 37784060: 37784060
23 EXOSC3 NM_016042.3(EXOSC3): c.155delC (p.Pro52Argfs) deletion Pathogenic rs886041316 GRCh37 Chromosome 9, 37784887: 37784887
24 EXOSC3 NM_016042.3(EXOSC3): c.155delC (p.Pro52Argfs) deletion Pathogenic rs886041316 GRCh38 Chromosome 9, 37784890: 37784890
25 EXOSC3 NM_016042.3(EXOSC3): c.540T> C (p.Cys180=) single nucleotide variant Benign/Likely benign rs62640003 GRCh37 Chromosome 9, 37782069: 37782069
26 EXOSC3 NM_016042.3(EXOSC3): c.540T> C (p.Cys180=) single nucleotide variant Benign/Likely benign rs62640003 GRCh38 Chromosome 9, 37782072: 37782072
27 EXOSC3 NM_016042.3(EXOSC3): c.588T> C (p.Asp196=) single nucleotide variant Likely benign rs147568068 GRCh37 Chromosome 9, 37782021: 37782021
28 EXOSC3 NM_016042.3(EXOSC3): c.588T> C (p.Asp196=) single nucleotide variant Likely benign rs147568068 GRCh38 Chromosome 9, 37782024: 37782024
29 EXOSC3 NM_016042.3(EXOSC3): c.475-12A> G single nucleotide variant Conflicting interpretations of pathogenicity rs370087266 GRCh37 Chromosome 9, 37782146: 37782146
30 EXOSC3 NM_016042.3(EXOSC3): c.475-12A> G single nucleotide variant Conflicting interpretations of pathogenicity rs370087266 GRCh38 Chromosome 9, 37782149: 37782149
31 EXOSC3 NM_016042.3(EXOSC3): c.782C> T (p.Thr261Met) single nucleotide variant Uncertain significance GRCh38 Chromosome 9, 37780725: 37780725
32 EXOSC3 NM_016042.3(EXOSC3): c.782C> T (p.Thr261Met) single nucleotide variant Uncertain significance GRCh37 Chromosome 9, 37780722: 37780722
33 VRK1 NM_003384.2(VRK1): c.156_160+3delTCTTGGTA deletion Likely pathogenic GRCh37 Chromosome 14, 97299964: 97299971
34 VRK1 NM_003384.2(VRK1): c.156_160+3delTCTTGGTA deletion Likely pathogenic GRCh38 Chromosome 14, 96833627: 96833634

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 EXOSC3 EXOSC8
2
Show member pathways
11.24 EXOSC3 EXOSC8
3
Show member pathways
10.38 EXOSC3 EXOSC8

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 exosome (RNase complex) GO:0000178 9.16 EXOSC3 EXOSC8
2 nuclear exosome (RNase complex) GO:0000176 8.96 EXOSC3 EXOSC8
3 cytoplasmic exosome (RNase complex) GO:0000177 8.62 EXOSC3 EXOSC8

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

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 EXOSC3 EXOSC8

Sources for Pontocerebellar Hypoplasia, Type 1b

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
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35 ICD10 via Orphanet
36 ICD9CM
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45 MeSH
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59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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