PCH1
MCID: PNT010
MIFTS: 42

Pontocerebellar Hypoplasia Type 1 (PCH1)

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 1

MalaCards integrated aliases for Pontocerebellar Hypoplasia Type 1:

Name: Pontocerebellar Hypoplasia Type 1 53 59 29 6 72
Pontocerebellar Hypoplasia with Infantile Spinal Muscular Atrophy 53
Pontocerebellar Hypoplasia with Anterior Horn Cell Disease 53
Hypoplasia, Pontocerebellar, Type 1 40
Norman Disease 59
Pch1 59

Characteristics:

Orphanet epidemiological data:

59
pontocerebellar hypoplasia type 1
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood,infantile;

Classifications:



External Ids:

MESH via Orphanet 45 C548069
ICD10 via Orphanet 34 Q04.3
UMLS via Orphanet 73 C1843504
Orphanet 59 ORPHA2254
UMLS 72 C1843504

Summaries for Pontocerebellar Hypoplasia Type 1

NIH Rare Diseases : 53 Pontocerebellar hypoplasia type 1 (PCH1) is a genetic disease that affects the development of the brain. Babies and children with this disease have an unusually small and underdeveloped cerebellum, which is the part of the brain that coordinates movement. A region of the brain called the pons also fails to develop properly. The pons, which is located at the base of the brain in an area called the brainstem, sends signals between the cerebellum and the rest of the brain. Individuals with PCH1 also experience a degeneration of the anterior horn cells, which are responsible for helping the spinal cord send signals to the muscles. Problems with the anterior horn cells cause severe muscle weakness. PCH1 is caused by mutations to EXOSC3, TSEN54, RARS2, and VRK1. The disease is inherited in an autosomal recessive manner. Diagnosis of PCH1 is based on brain imaging and tests to rule out other causes of problems with brain development. Treatment for PCH1 is aimed at relieving the symptoms of the disease. Most children with PCH1 pass away in infancy or early childhood.

MalaCards based summary : Pontocerebellar Hypoplasia Type 1, also known as pontocerebellar hypoplasia with infantile spinal muscular atrophy, is related to pontocerebellar hypoplasia, type 5 and pontocerebellar hypoplasia, type 6, and has symptoms including ataxia, muscle weakness and muscular fasciculation. An important gene associated with Pontocerebellar Hypoplasia Type 1 is VRK1 (VRK Serine/Threonine Kinase 1), and among its related pathways/superpathways are Gene Expression and rRNA processing in the nucleus and cytosol. Affiliated tissues include brain, testes and spinal cord, and related phenotype is Lamellipodia cells.

Related Diseases for Pontocerebellar Hypoplasia Type 1

Diseases in the Pontocerebellar Hypoplasia family:

Pontocerebellar Hypoplasia, Type 4 Pontocerebellar Hypoplasia, Type 2a
Pontocerebellar Hypoplasia, Type 1a Pontocerebellar Hypoplasia, Type 3
Pontocerebellar Hypoplasia, Type 5 Pontocerebellar Hypoplasia, Type 6
Pontocerebellar Hypoplasia, Type 2b Pontocerebellar Hypoplasia, Type 2c
Pontocerebellar Hypoplasia, Type 2d Pontocerebellar Hypoplasia, Type 1b
Pontocerebellar Hypoplasia, Type 8 Pontocerebellar Hypoplasia, Type 7
Pontocerebellar Hypoplasia, Type 10 Pontocerebellar Hypoplasia, Type 9
Pontocerebellar Hypoplasia, Type 2e Pontocerebellar Hypoplasia, Type 1c
Pontocerebellar Hypoplasia, Type 2f Pontocerebellar Hypoplasia, Type 11
Pontocerebellar Hypoplasia, Type 1d Pontocerebellar Hypoplasia, Type 12
Pontocerebellar Hypoplasia Type 1

Diseases related to Pontocerebellar Hypoplasia Type 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 53)
# Related Disease Score Top Affiliating Genes
1 pontocerebellar hypoplasia, type 5 31.3 VRK1 TSEN54
2 pontocerebellar hypoplasia, type 6 30.8 VRK1 TSEN54 RARS2
3 pontocerebellar hypoplasia, type 1b 30.1 EXOSC8 EXOSC3
4 microcephaly 29.2 VRK1 TSEN54 EXOSC3
5 pontocerebellar hypoplasia 28.7 VRK1 TSEN54 RARS2 EXOSC8 EXOSC3
6 pontocerebellar hypoplasia, type 1a 11.4
7 pontocerebellar hypoplasia, type 4 11.1
8 pontocerebellar hypoplasia, type 2a 11.1
9 pontocerebellar hypoplasia, type 3 11.1
10 pontocerebellar hypoplasia, type 2b 11.1
11 pontocerebellar hypoplasia, type 2c 11.1
12 pontocerebellar hypoplasia, type 8 11.1
13 pontocerebellar hypoplasia, type 7 11.1
14 pontocerebellar hypoplasia, type 10 11.1
15 pontocerebellar hypoplasia, type 9 11.1
16 pontocerebellar hypoplasia, type 11 11.1
17 spinal muscular atrophy 10.5
18 muscular atrophy 10.5
19 hypotonia 10.5
20 exosc3-related pontocerebellar hypoplasia 10.4
21 spinal muscular atrophy, type i 10.3
22 spinal muscular atrophy, x-linked 2 10.3
23 olivopontocerebellar atrophy 10.3
24 anterior horn cell disease 10.3
25 cavitary optic disc anomalies 10.2
26 ataxia and polyneuropathy, adult-onset 10.2
27 congenital disorders of n-linked glycosylation and multiple pathway 10.2
28 spinocerebellar ataxia 1 10.1
29 3-methylglutaconic aciduria, type iii 10.1
30 retinitis pigmentosa 10.1
31 neuropathy, ataxia, and retinitis pigmentosa 10.1
32 aceruloplasminemia 10.1
33 bainbridge-ropers syndrome 10.1
34 alkuraya-kucinskas syndrome 10.1
35 neuroretinitis 10.1
36 respiratory failure 10.1
37 autosomal dominant cerebellar ataxia 10.1
38 cerebral palsy 10.1
39 motor neuron disease 10.1
40 retinitis 10.1
41 dystonia 10.1
42 mitochondrial metabolism disease 10.1
43 axonal neuropathy 10.1
44 polyhydramnios 10.1
45 pathologic nystagmus 10.1
46 mitochondrial disorders 10.1
47 tsen54-related pontocerebellar hypoplasia 10.1
48 congenital contractures 10.1
49 dysphagia 10.1
50 hypertonia 10.1

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



Diseases related to Pontocerebellar Hypoplasia Type 1

Symptoms & Phenotypes for Pontocerebellar Hypoplasia Type 1

UMLS symptoms related to Pontocerebellar Hypoplasia Type 1:


ataxia, muscle weakness, muscular fasciculation, weakness

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

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Lamellipodia cells GR00165-A 8.8 EXOSC3 EXOSC8 TSEN54

Drugs & Therapeutics for Pontocerebellar Hypoplasia Type 1

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

Genetic Tests for Pontocerebellar Hypoplasia Type 1

Genetic tests related to Pontocerebellar Hypoplasia Type 1:

# Genetic test Affiliating Genes
1 Pontocerebellar Hypoplasia Type 1 29

Anatomical Context for Pontocerebellar Hypoplasia Type 1

MalaCards organs/tissues related to Pontocerebellar Hypoplasia Type 1:

41
Brain, Testes, Spinal Cord, Cerebellum, Pons

Publications for Pontocerebellar Hypoplasia Type 1

Articles related to Pontocerebellar Hypoplasia Type 1:

(show all 31)
# Title Authors PMID Year
1
Novel EXOSC3 mutation causes complicated hereditary spastic paraplegia. 38 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. 38 71
23883322 2013
3
Exome sequencing in a family with intellectual disability, early onset spasticity, and cerebellar atrophy detects a novel mutation in EXOSC3. 38 71
23975261 2013
4
Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration. 38 71
22544365 2012
5
Spinal muscular atrophy with pontocerebellar hypoplasia is caused by a mutation in the VRK1 gene. 38 71
19646678 2009
6
EXOSC3-Related Pontocerebellar Hypoplasia 71
25144110 2014
7
EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia. 71
24989451 2014
8
Deep sequencing reveals 50 novel genes for recessive cognitive disorders. 71
21937992 2011
9
Consensus statement for standard of care in spinal muscular atrophy. 71
17761659 2007
10
Biallelic variants in AGTPBP1, involved in tubulin deglutamylation, are associated with cerebellar degeneration and motor neuropathy. 38
30976113 2019
11
Expanded PCH1D phenotype linked to EXOSC9 mutation. 38
30690203 2019
12
De novo variant in KIF26B is associated with pontocerebellar hypoplasia with infantile spinal muscular atrophy. 38
30151950 2018
13
Pontocerebellar hypoplasia type 1 for the neuropediatrician: Genotype-phenotype correlations and diagnostic guidelines based on new cases and overview of the literature. 38
29656927 2018
14
Whole exome sequencing diagnoses the first fetal case of Bainbridge-Ropers syndrome presenting as pontocerebellar hypoplasia type 1. 38
29316359 2018
15
EXOSC3 mutations in pontocerebellar hypoplasia type 1: novel mutations and genotype-phenotype correlations. 38
24524299 2014
16
Pontocerebellar hypoplasia type 1 with a milder phenotype in a two-year-old girl. 38
24891912 2014
17
Pontocerebellar hypoplasia type 1: clinical spectrum and relevance of EXOSC3 mutations. 38
23284067 2013
18
TSEN54 mutation in a child with pontocerebellar hypoplasia type 1. 38
21468723 2011
19
Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. 38
20952379 2011
20
Autopsy case of later-onset pontocerebellar hypoplasia type 1: pontine atrophy and pyramidal tract involvement. 38
20558670 2010
21
Delayed gyration with pontocerebellar hypoplasia type 1. 38
19243903 2010
22
A mild variant of pontocerebellar hypoplasia type 1 in a 12-year-old Indian boy. 38
19302945 2009
23
Macrocephaly in association with pontocerebellar hypoplasia type 1: a paradox. 38
19359782 2009
24
Pontocerebellar hypoplasia type 1. 38
18805371 2008
25
Infantile onset progressive cerebellar atrophy and anterior horn cell degeneration--a late onset variant of PCH-1? 38
17681808 2008
26
[Pontocerebellar hypoplasia type 1: a case report]. 38
17342678 2007
27
Pontocerebellar hypoplasia type 1: new leads for an earlier diagnosis. 38
12731647 2003
28
Extended phenotype of pontocerebellar hypoplasia with infantile spinal muscular atrophy. 38
12548734 2003
29
Analysis and classification of cerebellar malformations. 38
12169461 2002
30
Pontocerebellar hypoplasia type 2 (PCH2): report of two siblings. 38
10814903 2000
31
Pontocerebellar hypoplasia associated with respiratory-chain defects. 38
10401692 1999

Variations for Pontocerebellar Hypoplasia Type 1

ClinVar genetic disease variations for Pontocerebellar Hypoplasia Type 1:

6 (show all 44)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 VRK1 NM_003384.3(VRK1): c.6del (p.Arg3fs) deletion Pathogenic rs780789145 14:97299814-97299814 14:96833477-96833477
2 VRK1 NM_003384.3(VRK1): c.1072C> T (p.Arg358Ter) single nucleotide variant Pathogenic rs137853063 14:97342370-97342370 14:96876033-96876033
3 VRK1 NC_000014.8: g.(?_97312412)_(97313701_?)del deletion Pathogenic 14:97312412-97313701 14:96846075-96847364
4 VRK1 NM_003384.3(VRK1): c.976C> T (p.Gln326Ter) single nucleotide variant Pathogenic 14:97326980-97326980 14:96860643-96860643
5 VRK1 NM_003384.3(VRK1): c.362_365del (p.Lys121fs) deletion Pathogenic 14:97313668-97313671 14:96847332-96847335
6 VRK1 NM_003384.3(VRK1): c.1066A> T (p.Lys356Ter) single nucleotide variant Pathogenic 14:97327070-97327070 14:96860733-96860733
7 VRK1 NC_000014.8: g.(?_97277006)_(97327082_?)del deletion Pathogenic 14:97277006-97327082 14:96810669-96860745
8 VRK1 NC_000014.8: g.(?_97322457)_(97327082_?)del deletion Pathogenic 14:97322457-97327082 14:96856120-96860745
9 VRK1 NM_003384.2(VRK1): c.318_889+1945del deletion Likely pathogenic 14:97313625-97324868 14:96847288-96858531
10 VRK1 NM_003384.3(VRK1): c.266G> A (p.Arg89Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs773138218 14:97312481-97312481 14:96846144-96846144
11 VRK1 NM_003384.3(VRK1): c.961C> T (p.Arg321Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs772731615 14:97326965-97326965 14:96860628-96860628
12 VRK1 NM_003384.3(VRK1): c.706G> A (p.Val236Met) single nucleotide variant Conflicting interpretations of pathogenicity rs771364038 14:97321690-97321690 14:96855353-96855353
13 VRK1 NM_003384.3(VRK1): c.882C> G (p.Asn294Lys) single nucleotide variant Uncertain significance rs541660707 14:97322916-97322916 14:96856579-96856579
14 VRK1 NM_003384.3(VRK1): c.901A> G (p.Lys301Glu) single nucleotide variant Uncertain significance rs149661915 14:97326905-97326905 14:96860568-96860568
15 VRK1 NM_003384.3(VRK1): c.7_8delinsTT (p.Arg3Phe) indel Uncertain significance 14:97299815-97299816 14:96833478-96833479
16 VRK1 NM_003384.3(VRK1): c.216+8A> G single nucleotide variant Uncertain significance 14:97304162-97304162 14:96837825-96837825
17 VRK1 NM_003384.3(VRK1): c.397C> T (p.Arg133Cys) single nucleotide variant Uncertain significance rs387906830 14:97319190-97319190 14:96852853-96852853
18 VRK1 NM_003384.3(VRK1): c.858G> T (p.Met286Ile) single nucleotide variant Uncertain significance rs139476915 14:97322892-97322892 14:96856555-96856555
19 VRK1 NM_003384.3(VRK1): c.1024_1025delinsCC (p.Ser342Pro) indel Uncertain significance 14:97327028-97327029 14:96860691-96860692
20 VRK1 NM_003384.3(VRK1): c.1180G> A (p.Val394Ile) single nucleotide variant Uncertain significance 14:97347534-97347534 14:96881197-96881197
21 VRK1 NM_003384.3(VRK1): c.607C> T (p.Arg203Trp) single nucleotide variant Uncertain significance 14:97321591-97321591 14:96855254-96855254
22 VRK1 NM_003384.3(VRK1): c.845T> C (p.Ile282Thr) single nucleotide variant Uncertain significance 14:97322879-97322879 14:96856542-96856542
23 VRK1 NM_003384.3(VRK1): c.863A> G (p.Lys288Arg) single nucleotide variant Uncertain significance 14:97322897-97322897 14:96856560-96856560
24 VRK1 NM_003384.3(VRK1): c.1106G> C (p.Gly369Ala) single nucleotide variant Uncertain significance 14:97342404-97342404 14:96876067-96876067
25 VRK1 NM_003384.3(VRK1): c.307C> T (p.Arg103Cys) single nucleotide variant Uncertain significance 14:97313614-97313614 14:96847277-96847277
26 VRK1 NM_003384.3(VRK1): c.944C> T (p.Pro315Leu) single nucleotide variant Uncertain significance 14:97326948-97326948 14:96860611-96860611
27 VRK1 NM_003384.3(VRK1): c.536A> G (p.Lys179Arg) single nucleotide variant Uncertain significance 14:97319463-97319463 14:96853126-96853126
28 VRK1 NM_003384.3(VRK1): c.772C> T (p.His258Tyr) single nucleotide variant Uncertain significance 14:97322529-97322529 14:96856192-96856192
29 VRK1 NM_003384.3(VRK1): c.362A> G (p.Lys121Arg) single nucleotide variant Uncertain significance rs1064796973 14:97313669-97313669 14:96847332-96847332
30 VRK1 NM_003384.3(VRK1): c.1021C> T (p.Leu341Phe) single nucleotide variant Uncertain significance rs139734064 14:97327025-97327025 14:96860688-96860688
31 VRK1 NM_003384.3(VRK1): c.1160G> A (p.Arg387His) single nucleotide variant Uncertain significance rs1420939606 14:97347514-97347514 14:96881177-96881177
32 VRK1 NM_003384.3(VRK1): c.26C> T (p.Ala9Val) single nucleotide variant Uncertain significance 14:97299834-97299834 14:96833497-96833497
33 VRK1 NM_003384.3(VRK1): c.8G> A (p.Arg3His) single nucleotide variant Uncertain significance 14:97299816-97299816 14:96833479-96833479
34 VRK1 NM_003384.3(VRK1): c.308G> A (p.Arg103His) single nucleotide variant Uncertain significance 14:97313615-97313615 14:96847278-96847278
35 VRK1 NM_003384.3(VRK1): c.1070A> T (p.Lys357Met) single nucleotide variant Uncertain significance 14:97342368-97342368 14:96876031-96876031
36 VRK1 NM_003384.3(VRK1): c.1123T> C (p.Trp375Arg) single nucleotide variant Uncertain significance 14:97342421-97342421 14:96876084-96876084
37 VRK1 NM_003384.3(VRK1): c.576+9A> G single nucleotide variant Uncertain significance 14:97319512-97319512 14:96853175-96853175
38 VRK1 NM_003384.3(VRK1): c.418A> G (p.Lys140Glu) single nucleotide variant Uncertain significance 14:97319211-97319211 14:96852874-96852874
39 VRK1 NM_003384.3(VRK1): c.683C> T (p.Thr228Met) single nucleotide variant Uncertain significance 14:97321667-97321667 14:96855330-96855330
40 VRK1 NM_003384.3(VRK1): c.701A> G (p.Asn234Ser) single nucleotide variant Uncertain significance 14:97321685-97321685 14:96855348-96855348
41 VRK1 NM_003384.3(VRK1): c.817G> C (p.Asp273His) single nucleotide variant Uncertain significance 14:97322574-97322574 14:96856237-96856237
42 VRK1 NM_003384.3(VRK1): c.860A> G (p.Asp287Gly) single nucleotide variant Uncertain significance 14:97322894-97322894 14:96856557-96856557
43 VRK1 NM_003384.3(VRK1): c.962G> A (p.Arg321His) single nucleotide variant Uncertain significance 14:97326966-97326966 14:96860629-96860629
44 VRK1 NM_003384.3(VRK1): c.161-3C> T single nucleotide variant Uncertain significance 14:97304096-97304096 14:96837759-96837759

Expression for Pontocerebellar Hypoplasia Type 1

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

Pathways for Pontocerebellar Hypoplasia Type 1

GO Terms for Pontocerebellar Hypoplasia Type 1

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

# Name GO ID Score Top Affiliating Genes
1 nucleoplasm GO:0005654 9.72 VRK1 TSEN54 EXOSC9 EXOSC8 EXOSC3
2 nucleolus GO:0005730 9.65 VRK1 TSEN54 EXOSC9 EXOSC8 EXOSC3
3 exosome (RNase complex) GO:0000178 9.33 EXOSC9 EXOSC8 EXOSC3
4 nuclear exosome (RNase complex) GO:0000176 9.13 EXOSC9 EXOSC8 EXOSC3
5 cytoplasmic exosome (RNase complex) GO:0000177 8.8 EXOSC9 EXOSC8 EXOSC3

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

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 rRNA processing GO:0006364 9.69 EXOSC9 EXOSC8 EXOSC3
2 regulation of mRNA stability GO:0043488 9.63 EXOSC9 EXOSC8 EXOSC3
3 exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay GO:0043928 9.54 EXOSC9 EXOSC8 EXOSC3
4 rRNA catabolic process GO:0016075 9.52 EXOSC9 EXOSC8
5 nuclear-transcribed mRNA catabolic process, exonucleolytic, 3'-5' GO:0034427 9.5 EXOSC9 EXOSC8 EXOSC3
6 nuclear mRNA surveillance GO:0071028 9.49 EXOSC9 EXOSC8
7 nuclear polyadenylation-dependent mRNA catabolic process GO:0071042 9.48 EXOSC9 EXOSC8
8 U5 snRNA 3'-end processing GO:0034476 9.43 EXOSC9 EXOSC8
9 U4 snRNA 3'-end processing GO:0034475 9.43 EXOSC9 EXOSC8 EXOSC3
10 U1 snRNA 3'-end processing GO:0034473 9.4 EXOSC9 EXOSC8
11 nuclear polyadenylation-dependent rRNA catabolic process GO:0071035 9.33 EXOSC9 EXOSC8 EXOSC3
12 nuclear polyadenylation-dependent tRNA catabolic process GO:0071038 9.13 EXOSC9 EXOSC8 EXOSC3
13 exonucleolytic trimming to generate mature 3'-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) GO:0000467 8.8 EXOSC9 EXOSC8 EXOSC3

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

# Name GO ID Score Top Affiliating Genes
1 RNA binding GO:0003723 9.56 RARS2 EXOSC9 EXOSC8 EXOSC3
2 3'-5'-exoribonuclease activity GO:0000175 9.16 EXOSC9 EXOSC3
3 AU-rich element binding GO:0017091 8.96 EXOSC9 EXOSC8
4 exoribonuclease activity GO:0004532 8.8 EXOSC9 EXOSC8 EXOSC3

Sources for Pontocerebellar Hypoplasia Type 1

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
Content
Loading form....