MCID: PNT018
MIFTS: 37

Pontocerebellar Hypoplasia, Type 1b

Categories: Genetic diseases, Neuronal diseases, Rare diseases, Fetal diseases, Muscle diseases, Eye diseases, Metabolic 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 73
Pontocerebellar Hypoplasia Type 1b 12 15
Pch1b 57 75
Hypoplasia, Pontocerebellar, Type 1b 40
Pontocerebellar Hypoplasia 1b 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset at birth
early death may occur


HPO:

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


Classifications:



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 spasticity and muscle weakness. An important gene associated with Pontocerebellar Hypoplasia, Type 1b is EXOSC3 (Exosome Component 3), and among its related pathways/superpathways are Purine metabolism (KEGG) and Unfolded Protein Response (UPR). Affiliated tissues include tongue, pons and skeletal muscle, and related phenotypes are progressive microcephaly and strabismus

UniProtKB/Swiss-Prot : 75 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.

Symptoms & Phenotypes for Pontocerebellar Hypoplasia, Type 1b

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

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

Human phenotypes related to Pontocerebellar Hypoplasia, Type 1b:

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

UMLS symptoms related to Pontocerebellar Hypoplasia, Type 1b:


muscle spasticity, muscle weakness

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, Pons, Skeletal Muscle, Spinal Cord

Publications for Pontocerebellar Hypoplasia, Type 1b

Articles related to Pontocerebellar Hypoplasia, Type 1b:

# Title Authors Year
1
Insight into the RNA Exosome Complex Through Modeling Pontocerebellar Hypoplasia Type 1b Disease Mutations in Yeast. ( 27777260 )
2017

Variations for Pontocerebellar Hypoplasia, Type 1b

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

75
# 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 24)
# Gene Variation Type Significance SNP ID Assembly Location
1 EXOSC3 NM_016042.3(EXOSC3): c.395A> C (p.Asp132Ala) single nucleotide variant Pathogenic/Likely pathogenic rs141138948 GRCh37 Chromosome 9, 37783990: 37783990
2 EXOSC3 NM_016042.3(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.571G> T (p.Gly191Cys) single nucleotide variant Pathogenic rs730882145 GRCh37 Chromosome 9, 37782038: 37782038
16 EXOSC3 NM_016042.3(EXOSC3): c.571G> T (p.Gly191Cys) single nucleotide variant Pathogenic rs730882145 GRCh38 Chromosome 9, 37782041: 37782041
17 EXOSC3 NM_016042.3(EXOSC3): c.572G> A (p.Gly191Asp) single nucleotide variant Conflicting interpretations of pathogenicity rs797045567 GRCh38 Chromosome 9, 37782040: 37782040
18 EXOSC3 NM_016042.3(EXOSC3): c.572G> A (p.Gly191Asp) single nucleotide variant Conflicting interpretations of pathogenicity rs797045567 GRCh37 Chromosome 9, 37782037: 37782037
19 EXOSC3 NM_016042.3(EXOSC3): c.155delC (p.Pro52Argfs) deletion Pathogenic rs886041316 GRCh37 Chromosome 9, 37784887: 37784887
20 EXOSC3 NM_016042.3(EXOSC3): c.155delC (p.Pro52Argfs) deletion Pathogenic rs886041316 GRCh38 Chromosome 9, 37784890: 37784890
21 EXOSC3 NM_016042.3(EXOSC3): c.540T> C (p.Cys180=) single nucleotide variant Benign/Likely benign rs62640003 GRCh37 Chromosome 9, 37782069: 37782069
22 EXOSC3 NM_016042.3(EXOSC3): c.540T> C (p.Cys180=) single nucleotide variant Benign/Likely benign rs62640003 GRCh38 Chromosome 9, 37782072: 37782072
23 EXOSC3 NM_016042.3(EXOSC3): c.588T> C (p.Asp196=) single nucleotide variant Likely benign rs147568068 GRCh37 Chromosome 9, 37782021: 37782021
24 EXOSC3 NM_016042.3(EXOSC3): c.588T> C (p.Asp196=) single nucleotide variant Likely benign rs147568068 GRCh38 Chromosome 9, 37782024: 37782024

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 exosome (RNase complex) GO:0000178 9.16 EXOSC3 EXOSC8
2 cytoplasmic exosome (RNase complex) GO:0000177 8.96 EXOSC3 EXOSC8
3 nuclear exosome (RNase complex) GO:0000176 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 U4 snRNA 3-end processing GO:0034475 9.26 EXOSC3 EXOSC8
6 exonucleolytic trimming to generate mature 3-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) GO:0000467 9.16 EXOSC3 EXOSC8
7 nuclear polyadenylation-dependent rRNA catabolic process GO:0071035 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 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
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