PCH1
MCID: PNT010
MIFTS: 39

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 6 73
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:

Orphanet 59 ORPHA2254
MESH via Orphanet 45 C548069
UMLS via Orphanet 74 C1843504
ICD10 via Orphanet 34 Q04.3
UMLS 73 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 weakness. 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 phenotypes are Increased shRNA abundance (Z-score > 2) and Increased shRNA abundance (Z-score > 2)

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 Exosc3-Related Pontocerebellar Hypoplasia
Tsen54-Related Pontocerebellar Hypoplasia Pontocerebellar Hypoplasia Type 1

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

(show all 20)
# Related Disease Score Top Affiliating Genes
1 pontocerebellar hypoplasia, type 5 31.3 TSEN54 VRK1
2 pontocerebellar hypoplasia, type 6 31.1 RARS2 TSEN54 VRK1
3 pontocerebellar hypoplasia 29.9 EXOSC3 EXOSC8 RARS2 TSEN54 VRK1
4 pontocerebellar hypoplasia, type 1a 11.2
5 pontocerebellar hypoplasia, type 4 11.0
6 pontocerebellar hypoplasia, type 2a 11.0
7 pontocerebellar hypoplasia, type 3 11.0
8 pontocerebellar hypoplasia, type 2b 11.0
9 pontocerebellar hypoplasia, type 2c 11.0
10 pontocerebellar hypoplasia, type 8 11.0
11 pontocerebellar hypoplasia, type 7 11.0
12 pontocerebellar hypoplasia, type 10 11.0
13 pontocerebellar hypoplasia, type 9 11.0
14 pontocerebellar hypoplasia, type 11 11.0
15 spinal muscular atrophy 10.2
16 muscular atrophy 10.2
17 bainbridge-ropers syndrome 10.1
18 pontocerebellar hypoplasia, type 1b 9.8 EXOSC3 EXOSC8
19 microcephaly 9.7 EXOSC3 TSEN54 VRK1
20 pontoneocerebellar hypoplasia 9.6 EXOSC3 RARS2 TSEN54 VRK1

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, weakness, muscular fasciculation

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

26 (show all 15)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-108 9.83 EXOSC8
2 Increased shRNA abundance (Z-score > 2) GR00366-A-126 9.83 EXOSC9
3 Increased shRNA abundance (Z-score > 2) GR00366-A-131 9.83 EXOSC9
4 Increased shRNA abundance (Z-score > 2) GR00366-A-146 9.83 EXOSC8
5 Increased shRNA abundance (Z-score > 2) GR00366-A-156 9.83 EXOSC8
6 Increased shRNA abundance (Z-score > 2) GR00366-A-157 9.83 EXOSC8 EXOSC9
7 Increased shRNA abundance (Z-score > 2) GR00366-A-159 9.83 EXOSC8
8 Increased shRNA abundance (Z-score > 2) GR00366-A-166 9.83 EXOSC8
9 Increased shRNA abundance (Z-score > 2) GR00366-A-177 9.83 EXOSC9
10 Increased shRNA abundance (Z-score > 2) GR00366-A-201 9.83 EXOSC8
11 Increased shRNA abundance (Z-score > 2) GR00366-A-73 9.83 EXOSC9
12 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.83 EXOSC9
13 Increased shRNA abundance (Z-score > 2) GR00366-A-9 9.83 EXOSC9
14 Increased shRNA abundance (Z-score > 2) GR00366-A-99 9.83 EXOSC9
15 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

Anatomical Context for Pontocerebellar Hypoplasia Type 1

MalaCards organs/tissues related to Pontocerebellar Hypoplasia Type 1:

41
Brain, Testes, Spinal Cord, Cerebellum, Pons, Eye

Publications for Pontocerebellar Hypoplasia Type 1

Articles related to Pontocerebellar Hypoplasia Type 1:

(show all 14)
# Title Authors Year
1
Whole exome sequencing diagnoses the first fetal case of Bainbridge-Ropers syndrome presenting as pontocerebellar hypoplasia type 1. ( 29316359 )
2018
2
Pontocerebellar hypoplasia type 1 for the neuropediatrician: Genotype-phenotype correlations and diagnostic guidelines based on new cases and overview of the literature. ( 29656927 )
2018
3
De novo variant in KIF26B is associated with pontocerebellar hypoplasia with infantile spinal muscular atrophy. ( 30151950 )
2018
4
EXOSC3 mutations in pontocerebellar hypoplasia type 1: novel mutations and genotype-phenotype correlations. ( 24524299 )
2014
5
Pontocerebellar hypoplasia type 1 with a milder phenotype in a two-year-old girl. ( 24891912 )
2014
6
Pontocerebellar hypoplasia type 1: clinical spectrum and relevance of EXOSC3 mutations. ( 23284067 )
2013
7
Homozygous EXOSC3 mutation c.92G→C, p.G31A is a founder mutation causing severe pontocerebellar hypoplasia type 1 among the Czech Roma. ( 23883322 )
2013
8
TSEN54 mutation in a child with pontocerebellar hypoplasia type 1. ( 21468723 )
2011
9
Autopsy case of later-onset pontocerebellar hypoplasia type 1: pontine atrophy and pyramidal tract involvement. ( 20558670 )
2010
10
Delayed gyration with pontocerebellar hypoplasia type 1. ( 19243903 )
2010
11
Macrocephaly in association with pontocerebellar hypoplasia type 1: a paradox. ( 19359782 )
2009
12
A mild variant of pontocerebellar hypoplasia type 1 in a 12-year-old Indian boy. ( 19302945 )
2009
13
Pontocerebellar hypoplasia type 1. ( 18805371 )
2008
14
Pontocerebellar hypoplasia type 1: new leads for an earlier diagnosis. ( 12731647 )
2003

Variations for Pontocerebellar Hypoplasia Type 1

ClinVar genetic disease variations for Pontocerebellar Hypoplasia Type 1:

6 (show all 48)
# Gene Variation Type Significance SNP ID Assembly Location
1 VRK1 NM_003384.2(VRK1): c.1072C> T (p.Arg358Ter) single nucleotide variant Pathogenic rs137853063 GRCh37 Chromosome 14, 97342370: 97342370
2 VRK1 NM_003384.2(VRK1): c.1072C> T (p.Arg358Ter) single nucleotide variant Pathogenic rs137853063 GRCh38 Chromosome 14, 96876033: 96876033
3 VRK1 NM_003384.2(VRK1): c.397C> T (p.Arg133Cys) single nucleotide variant Uncertain significance rs387906830 GRCh37 Chromosome 14, 97319190: 97319190
4 VRK1 NM_003384.2(VRK1): c.397C> T (p.Arg133Cys) single nucleotide variant Uncertain significance rs387906830 GRCh38 Chromosome 14, 96852853: 96852853
5 VRK1 NM_003384.2(VRK1): c.858G> T (p.Met286Ile) single nucleotide variant Uncertain significance rs139476915 GRCh37 Chromosome 14, 97322892: 97322892
6 VRK1 NM_003384.2(VRK1): c.858G> T (p.Met286Ile) single nucleotide variant Uncertain significance rs139476915 GRCh38 Chromosome 14, 96856555: 96856555
7 VRK1 NM_003384.2(VRK1): c.266G> A (p.Arg89Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs773138218 GRCh37 Chromosome 14, 97312481: 97312481
8 VRK1 NM_003384.2(VRK1): c.266G> A (p.Arg89Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs773138218 GRCh38 Chromosome 14, 96846144: 96846144
9 VRK1 NM_003384.2(VRK1): c.961C> T (p.Arg321Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs772731615 GRCh37 Chromosome 14, 97326965: 97326965
10 VRK1 NM_003384.2(VRK1): c.961C> T (p.Arg321Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs772731615 GRCh38 Chromosome 14, 96860628: 96860628
11 VRK1 NM_003384.2(VRK1): c.706G> A (p.Val236Met) single nucleotide variant Conflicting interpretations of pathogenicity rs771364038 GRCh38 Chromosome 14, 96855353: 96855353
12 VRK1 NM_003384.2(VRK1): c.706G> A (p.Val236Met) single nucleotide variant Conflicting interpretations of pathogenicity rs771364038 GRCh37 Chromosome 14, 97321690: 97321690
13 VRK1 NM_003384.2(VRK1): c.901A> G (p.Lys301Glu) single nucleotide variant Uncertain significance rs149661915 GRCh38 Chromosome 14, 96860568: 96860568
14 VRK1 NM_003384.2(VRK1): c.901A> G (p.Lys301Glu) single nucleotide variant Uncertain significance rs149661915 GRCh37 Chromosome 14, 97326905: 97326905
15 VRK1 NM_003384.2(VRK1): c.1021C> T (p.Leu341Phe) single nucleotide variant Uncertain significance rs139734064 GRCh38 Chromosome 14, 96860688: 96860688
16 VRK1 NM_003384.2(VRK1): c.1021C> T (p.Leu341Phe) single nucleotide variant Uncertain significance rs139734064 GRCh37 Chromosome 14, 97327025: 97327025
17 VRK1 NM_003384.2(VRK1): c.1160G> A (p.Arg387His) single nucleotide variant Uncertain significance GRCh38 Chromosome 14, 96881177: 96881177
18 VRK1 NM_003384.2(VRK1): c.1160G> A (p.Arg387His) single nucleotide variant Uncertain significance GRCh37 Chromosome 14, 97347514: 97347514
19 VRK1 NM_003384.2(VRK1): c.6delT (p.Arg3Valfs) deletion Pathogenic GRCh38 Chromosome 14, 96833477: 96833477
20 VRK1 NM_003384.2(VRK1): c.6delT (p.Arg3Valfs) deletion Pathogenic GRCh37 Chromosome 14, 97299814: 97299814
21 VRK1 NM_003384.2(VRK1): c.7_8delCGinsTT (p.Arg3Phe) indel Uncertain significance GRCh38 Chromosome 14, 96833478: 96833479
22 VRK1 NM_003384.2(VRK1): c.7_8delCGinsTT (p.Arg3Phe) indel Uncertain significance GRCh37 Chromosome 14, 97299815: 97299816
23 VRK1 NM_003384.2(VRK1): c.216+8A> G single nucleotide variant Uncertain significance rs369680885 GRCh38 Chromosome 14, 96837825: 96837825
24 VRK1 NM_003384.2(VRK1): c.216+8A> G single nucleotide variant Uncertain significance rs369680885 GRCh37 Chromosome 14, 97304162: 97304162
25 VRK1 NM_003384.2(VRK1): c.318_889+1945del deletion Likely pathogenic GRCh38 Chromosome 14, 96847288: 96858531
26 VRK1 NM_003384.2(VRK1): c.318_889+1945del deletion Likely pathogenic GRCh37 Chromosome 14, 97313625: 97324868
27 VRK1 NM_003384.2(VRK1): c.536A> G (p.Lys179Arg) single nucleotide variant Uncertain significance GRCh37 Chromosome 14, 97319463: 97319463
28 VRK1 NM_003384.2(VRK1): c.536A> G (p.Lys179Arg) single nucleotide variant Uncertain significance GRCh38 Chromosome 14, 96853126: 96853126
29 VRK1 NM_003384.2(VRK1): c.772C> T (p.His258Tyr) single nucleotide variant Uncertain significance rs761905254 GRCh37 Chromosome 14, 97322529: 97322529
30 VRK1 NM_003384.2(VRK1): c.772C> T (p.His258Tyr) single nucleotide variant Uncertain significance rs761905254 GRCh38 Chromosome 14, 96856192: 96856192
31 VRK1 NC_000014.9: g.(?_96846075)_(96847364_?)del deletion Pathogenic GRCh37 Chromosome 14, 97312412: 97313701
32 VRK1 NC_000014.9: g.(?_96846075)_(96847364_?)del deletion Pathogenic GRCh38 Chromosome 14, 96846075: 96847364
33 VRK1 NM_003384.2(VRK1): c.1024_1025delAGinsCC (p.Ser342Pro) indel Uncertain significance GRCh37 Chromosome 14, 97327028: 97327029
34 VRK1 NM_003384.2(VRK1): c.1024_1025delAGinsCC (p.Ser342Pro) indel Uncertain significance GRCh38 Chromosome 14, 96860691: 96860692
35 VRK1 NM_003384.2(VRK1): c.1180G> A (p.Val394Ile) single nucleotide variant Uncertain significance GRCh37 Chromosome 14, 97347534: 97347534
36 VRK1 NM_003384.2(VRK1): c.1180G> A (p.Val394Ile) single nucleotide variant Uncertain significance GRCh38 Chromosome 14, 96881197: 96881197
37 VRK1 NM_003384.2(VRK1): c.607C> T (p.Arg203Trp) single nucleotide variant Uncertain significance rs144600646 GRCh38 Chromosome 14, 96855254: 96855254
38 VRK1 NM_003384.2(VRK1): c.607C> T (p.Arg203Trp) single nucleotide variant Uncertain significance rs144600646 GRCh37 Chromosome 14, 97321591: 97321591
39 VRK1 NM_003384.2(VRK1): c.845T> C (p.Ile282Thr) single nucleotide variant Uncertain significance rs371024271 GRCh38 Chromosome 14, 96856542: 96856542
40 VRK1 NM_003384.2(VRK1): c.845T> C (p.Ile282Thr) single nucleotide variant Uncertain significance rs371024271 GRCh37 Chromosome 14, 97322879: 97322879
41 VRK1 NM_003384.2(VRK1): c.863A> G (p.Lys288Arg) single nucleotide variant Uncertain significance GRCh38 Chromosome 14, 96856560: 96856560
42 VRK1 NM_003384.2(VRK1): c.863A> G (p.Lys288Arg) single nucleotide variant Uncertain significance GRCh37 Chromosome 14, 97322897: 97322897
43 VRK1 NM_003384.2(VRK1): c.1106G> C (p.Gly369Ala) single nucleotide variant Uncertain significance GRCh38 Chromosome 14, 96876067: 96876067
44 VRK1 NM_003384.2(VRK1): c.1106G> C (p.Gly369Ala) single nucleotide variant Uncertain significance GRCh37 Chromosome 14, 97342404: 97342404
45 VRK1 NM_003384.2(VRK1): c.307C> T (p.Arg103Cys) single nucleotide variant Uncertain significance rs755450815 GRCh38 Chromosome 14, 96847277: 96847277
46 VRK1 NM_003384.2(VRK1): c.307C> T (p.Arg103Cys) single nucleotide variant Uncertain significance rs755450815 GRCh37 Chromosome 14, 97313614: 97313614
47 VRK1 NM_003384.2(VRK1): c.944C> T (p.Pro315Leu) single nucleotide variant Uncertain significance rs761494436 GRCh38 Chromosome 14, 96860611: 96860611
48 VRK1 NM_003384.2(VRK1): c.944C> T (p.Pro315Leu) single nucleotide variant Uncertain significance rs761494436 GRCh37 Chromosome 14, 97326948: 97326948

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 EXOSC3 EXOSC8 EXOSC9 TSEN54 VRK1
2 nucleolus GO:0005730 9.65 EXOSC3 EXOSC8 EXOSC9 TSEN54 VRK1
3 exosome (RNase complex) GO:0000178 9.33 EXOSC3 EXOSC8 EXOSC9
4 nuclear exosome (RNase complex) GO:0000176 9.13 EXOSC3 EXOSC8 EXOSC9
5 cytoplasmic exosome (RNase complex) GO:0000177 8.8 EXOSC3 EXOSC8 EXOSC9

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

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 EXOSC3 EXOSC8 EXOSC9 RARS2
2 3'-5'-exoribonuclease activity GO:0000175 9.16 EXOSC3 EXOSC9
3 AU-rich element binding GO:0017091 8.96 EXOSC8 EXOSC9
4 exoribonuclease activity GO:0004532 8.8 EXOSC3 EXOSC8 EXOSC9

Sources for Pontocerebellar Hypoplasia Type 1

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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