PCH1A
MCID: PNT045
MIFTS: 40

Pontocerebellar Hypoplasia, Type 1a (PCH1A)

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 1a

MalaCards integrated aliases for Pontocerebellar Hypoplasia, Type 1a:

Name: Pontocerebellar Hypoplasia, Type 1a 56
Pontocerebellar Hypoplasia Type 1a 56 12 29 13 6 15
Pontocerebellar Hypoplasia with Infantile Spinal Muscular Atrophy 56 73
Pontocerebellar Hypoplasia with Anterior Horn Cell Disease 56 73
Pch1a 56 73
Pontocerebellar Hypoplasia Type 1 71
Pontocerebellar Hypoplasia 1a 73
Pch1 56

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset prenatally or at birth
death often occurs in childhood
clinically resembles spinal muscular atrophy-1 (sma1, )


HPO:

31
pontocerebellar hypoplasia, type 1a:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive congenital onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0060265
OMIM 56 607596
OMIM Phenotypic Series 56 PS607596
MeSH 43 D002526
MedGen 41 C1843504
UMLS 71 C1843504

Summaries for Pontocerebellar Hypoplasia, Type 1a

OMIM : 56 Pontocerebellar hypoplasia (PCH) refers to a group of severe neurodegenerative disorders affecting growth and function of the brainstem and cerebellum, resulting in little or no development. Different types were classified based on the clinical picture and the spectrum of pathologic changes. PCH type 1 is characterized by central and peripheral motor dysfunction associated with anterior horn cell degeneration resembling infantile spinal muscular atrophy (SMA; see SMA1, 253300); death usually occurs early. (607596)

MalaCards based summary : Pontocerebellar Hypoplasia, Type 1a, also known as pontocerebellar hypoplasia type 1a, is related to pontocerebellar hypoplasia, type 1b and pontocerebellar hypoplasia, and has symptoms including ataxia, muscle weakness and muscular fasciculation. An important gene associated with Pontocerebellar Hypoplasia, Type 1a is VRK1 (VRK Serine/Threonine Kinase 1), and among its related pathways/superpathways are ECM proteoglycans and Nuclear Envelope Reassembly. Affiliated tissues include cerebellum, spinal cord and pons, and related phenotypes are intellectual disability and hyperreflexia

Disease Ontology : 12 A pontocerebellar hypoplasia that is characterized by central and peripheral motor dysfunction, hypotonia, spasticity and failure to thrive, has material basis in mutation in the VRK1 gene.

UniProtKB/Swiss-Prot : 73 Pontocerebellar hypoplasia 1A: A disorder characterized by an abnormally small cerebellum and brainstem, central and peripheral motor dysfunction from birth, gliosis and spinal cord anterior horn cells degeneration resembling infantile spinal muscular atrophy. Additional features include muscle hypotonia, congenital contractures and respiratory insufficiency that is evident at birth.

Related Diseases for Pontocerebellar Hypoplasia, Type 1a

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

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

(show all 32)
# Related Disease Score Top Affiliating Genes
1 pontocerebellar hypoplasia, type 1b 31.7 VRK1 SGSM1
2 pontocerebellar hypoplasia 31.3 VRK1 VLDLR LAMA2 CHMP1A
3 pontocerebellar hypoplasia, type 8 27.7 VRK2 VRK1 VLDLR OPHN1 LAMA2 LAMA1
4 pontocerebellar hypoplasia type 1 12.0
5 pontocerebellar hypoplasia, type 1c 11.2
6 pontocerebellar hypoplasia, type 1d 11.2
7 pontocerebellar hypoplasia, type 13 11.2
8 pontocerebellar hypoplasia, type 4 11.1
9 pontocerebellar hypoplasia, type 2a 11.1
10 pontocerebellar hypoplasia, type 3 11.1
11 pontocerebellar hypoplasia, type 5 11.1
12 pontocerebellar hypoplasia, type 6 11.1
13 pontocerebellar hypoplasia, type 2b 11.1
14 pontocerebellar hypoplasia, type 2c 11.1
15 pontocerebellar hypoplasia, type 7 11.1
16 pontocerebellar hypoplasia, type 10 11.1
17 pontocerebellar hypoplasia, type 9 11.1
18 pontocerebellar hypoplasia, type 11 11.1
19 spinal muscular atrophy 10.4
20 muscular atrophy 10.4
21 spinal muscular atrophy, type i 10.3
22 spinal muscular atrophy, x-linked 2 10.3
23 alkuraya-kucinskas syndrome 10.3
24 microcephaly 10.3
25 olivopontocerebellar atrophy 10.3
26 anterior horn cell disease 10.3
27 hypotonia 10.3
28 congenital amyoplasia 10.3
29 cavitary optic disc anomalies 10.2
30 muscular dystrophy, congenital, due to integrin alpha-7 deficiency 9.5 LAMA2 LAMA1
31 cerebellar hypoplasia 9.5 VLDLR OPHN1
32 strabismus 8.8 VLDLR OPHN1 LAMA1

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



Diseases related to Pontocerebellar Hypoplasia, Type 1a

Symptoms & Phenotypes for Pontocerebellar Hypoplasia, Type 1a

Human phenotypes related to Pontocerebellar Hypoplasia, Type 1a:

31 (show all 21)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 HP:0001249
2 hyperreflexia 31 HP:0001347
3 ataxia 31 HP:0001251
4 muscular hypotonia 31 HP:0001252
5 muscle weakness 31 HP:0001324
6 respiratory insufficiency 31 HP:0002093
7 global developmental delay 31 HP:0001263
8 feeding difficulties in infancy 31 HP:0008872
9 generalized hypotonia 31 HP:0001290
10 spinal muscular atrophy 31 HP:0007269
11 abnormality of the foot 31 HP:0001760
12 cerebellar hypoplasia 31 HP:0001321
13 hypoplasia of the pons 31 HP:0012110
14 fasciculations 31 HP:0002380
15 congenital contracture 31 HP:0002803
16 emg: neuropathic changes 31 HP:0003445
17 neuronal loss in basal ganglia 31 HP:0200147
18 psychomotor retardation 31 HP:0025356
19 degeneration of anterior horn cells 31 HP:0002398
20 basal ganglia gliosis 31 HP:0006999
21 hypoplasia of the ventral pons 31 HP:0006850

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
hyperreflexia
ataxia
neuronal loss in basal ganglia
psychomotor retardation
weakness
more
Respiratory:
respiratory insufficiency

Skeletal Feet:
foot deformities

Muscle Soft Tissue:
muscle weakness
fasciculations

Growth Other:
poor feeding

Skeletal:
congenital contractures

Clinical features from OMIM:

607596

UMLS symptoms related to Pontocerebellar Hypoplasia, Type 1a:


ataxia, muscle weakness, muscular fasciculation, weakness

Drugs & Therapeutics for Pontocerebellar Hypoplasia, Type 1a

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

Genetic Tests for Pontocerebellar Hypoplasia, Type 1a

Genetic tests related to Pontocerebellar Hypoplasia, Type 1a:

# Genetic test Affiliating Genes
1 Pontocerebellar Hypoplasia Type 1a 29 VRK1

Anatomical Context for Pontocerebellar Hypoplasia, Type 1a

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

40
Cerebellum, Spinal Cord, Pons, Eye

Publications for Pontocerebellar Hypoplasia, Type 1a

Articles related to Pontocerebellar Hypoplasia, Type 1a:

# Title Authors PMID Year
1
Deep sequencing reveals 50 novel genes for recessive cognitive disorders. 56 6
21937992 2011
2
Spinal muscular atrophy with pontocerebellar hypoplasia is caused by a mutation in the VRK1 gene. 56 6
19646678 2009
3
Autosomal recessive mental retardation: homozygosity mapping identifies 27 single linkage intervals, at least 14 novel loci and several mutation hotspots. 56
21063731 2011
4
Consensus statement for standard of care in spinal muscular atrophy. 6
17761659 2007
5
Extended phenotype of pontocerebellar hypoplasia with infantile spinal muscular atrophy. 56
12548734 2003
6
Pontocerebellar hypoplasias. An overview of a group of inherited neurodegenerative disorders with fetal onset. 56
8147499 1993
7
Infantile olivopontocerebellar atrophy with spinal muscular atrophy (infantile OPCA + SMA). 56
2407400 1990
8
Cerebellar hypoplasia in Werdnig-Hoffmann disease. 56
13729575 1961
9
Infantile onset progressive cerebellar atrophy and anterior horn cell Degeneration-A novel phenotype associated with mutations in the PLA2G6 gene. 61
31689548 2019
10
Effect of in situ expression of human interleukin-6 on antibody responses against Salmonella typhimurium antigens. 61
12832117 2003

Variations for Pontocerebellar Hypoplasia, Type 1a

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

6 (show all 22) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 VRK1 NM_003384.3(VRK1):c.1072C>T (p.Arg358Ter)SNV Pathogenic 7497 rs137853063 14:97342370-97342370 14:96876033-96876033
2 VRK1 NM_003384.3(VRK1):c.879_882AAAC[1] (p.Lys295fs)short repeat Pathogenic 464942 rs779282547 14:97322913-97322916 14:96856576-96856579
3 CHMP1A NM_002768.5(CHMP1A):c.346G>A (p.Glu116Lys)SNV Pathogenic 522948 rs1064794609 16:89713646-89713646 16:89647238-89647238
4 VRK1 NM_003384.3(VRK1):c.265C>T (p.Arg89Ter)SNV Pathogenic 533537 rs772263867 14:97312480-97312480 14:96846143-96846143
5 VRK1 NM_003384.3(VRK1):c.976C>T (p.Gln326Ter)SNV Pathogenic 619220 rs1566713184 14:97326980-97326980 14:96860643-96860643
6 VRK1 NM_003384.3(VRK1):c.356A>G (p.His119Arg)SNV Likely pathogenic 209204 rs371295780 14:97313663-97313663 14:96847326-96847326
7 VRK1 NM_003384.3(VRK1):c.961C>T (p.Arg321Cys)SNV Conflicting interpretations of pathogenicity 209205 rs772731615 14:97326965-97326965 14:96860628-96860628
8 VRK1 NM_003384.3(VRK1):c.266G>A (p.Arg89Gln)SNV Conflicting interpretations of pathogenicity 197213 rs773138218 14:97312481-97312481 14:96846144-96846144
9 VRK1 NM_003384.3(VRK1):c.706G>A (p.Val236Met)SNV Conflicting interpretations of pathogenicity 218924 rs771364038 14:97321690-97321690 14:96855353-96855353
10 VRK1 NM_003384.3(VRK1):c.1150A>G (p.Ile384Val)SNV Uncertain significance 212586 rs147604836 14:97342448-97342448 14:96876111-96876111
11 VRK1 NM_003384.3(VRK1):c.397C>T (p.Arg133Cys)SNV Uncertain significance 30243 rs387906830 14:97319190-97319190 14:96852853-96852853
12 VRK1 NM_003384.3(VRK1):c.585G>C (p.Leu195Phe)SNV Uncertain significance 533534 rs748878251 14:97321569-97321569 14:96855232-96855232
13 VRK1 NM_003384.3(VRK1):c.668G>T (p.Gly223Val)SNV Uncertain significance 533535 rs1555361508 14:97321652-97321652 14:96855315-96855315
14 VRK1 NM_003384.3(VRK1):c.134A>G (p.Gln45Arg)SNV Uncertain significance 533536 rs1372198425 14:97299942-97299942 14:96833605-96833605
15 VRK1 NM_003384.3(VRK1):c.704G>A (p.Gly235Asp)SNV Uncertain significance 464941 rs1311364931 14:97321688-97321688 14:96855351-96855351
16 VRK1 NM_003384.3(VRK1):c.1174_1177del (p.Lys392fs)deletion Uncertain significance 632224 rs749258908 14:97347525-97347528 14:96881188-96881191
17 VRK1 NM_003384.3(VRK1):c.398G>A (p.Arg133His)SNV Uncertain significance 638314 14:97319191-97319191 14:96852854-96852854
18 VRK1 NM_003384.3(VRK1):c.397C>G (p.Arg133Gly)SNV Uncertain significance 800521 14:97319190-97319190 14:96852853-96852853
19 VRK1 NM_003384.3(VRK1):c.901A>G (p.Lys301Glu)SNV Uncertain significance 315123 rs149661915 14:97326905-97326905 14:96860568-96860568
20 VRK1 NM_003384.3(VRK1):c.1164A>C (p.Ser388=)SNV Likely benign 533539 rs760801260 14:97347518-97347518 14:96881181-96881181
21 VRK1 NM_003384.3(VRK1):c.45A>G (p.Ala15=)SNV Benign 130731 rs2145635 14:97299853-97299853 14:96833516-96833516
22 VRK1 NM_003384.3(VRK1):c.705C>T (p.Gly235=)SNV Benign 130732 rs2230532 14:97321689-97321689 14:96855352-96855352

Expression for Pontocerebellar Hypoplasia, Type 1a

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

Pathways for Pontocerebellar Hypoplasia, Type 1a

Pathways related to Pontocerebellar Hypoplasia, Type 1a according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.71 LAMA2 LAMA1
2
Show member pathways
10.14 VRK2 VRK1

GO Terms for Pontocerebellar Hypoplasia, Type 1a

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

# Name GO ID Score Top Affiliating Genes
1 multivesicular body GO:0005771 8.96 CHMP1B CHMP1A
2 ESCRT III complex GO:0000815 8.62 CHMP1B CHMP1A

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

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of GTPase activity GO:0043547 9.74 SGSM1 OPHN1 ARHGAP42
2 regulation of cell adhesion GO:0030155 9.56 LAMA2 LAMA1
3 tissue development GO:0009888 9.55 LAMA2 LAMA1
4 mitotic metaphase plate congression GO:0007080 9.54 CHMP1B CHMP1A
5 multivesicular body assembly GO:0036258 9.52 CHMP1B CHMP1A
6 nucleus organization GO:0006997 9.51 CHMP1B CHMP1A
7 regulation of mitotic spindle assembly GO:1901673 9.49 CHMP1B CHMP1A
8 viral budding via host ESCRT complex GO:0039702 9.48 CHMP1B CHMP1A
9 regulation of embryonic development GO:0045995 9.46 LAMA2 LAMA1
10 regulation of centrosome duplication GO:0010824 9.43 CHMP1B CHMP1A
11 midbody abscission GO:0061952 9.4 CHMP1B CHMP1A
12 vacuolar transport GO:0007034 9.37 CHMP1B CHMP1A
13 establishment of epithelial cell apical/basal polarity GO:0045198 9.32 OPHN1 LAMA1
14 endosome transport via multivesicular body sorting pathway GO:0032509 9.26 CHMP1B CHMP1A
15 ESCRT III complex disassembly GO:1904903 9.16 CHMP1B CHMP1A
16 late endosome to vacuole transport GO:0045324 8.96 CHMP1B CHMP1A
17 axon guidance GO:0007411 8.92 VLDLR OPHN1 LAMA2 LAMA1

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

# Name GO ID Score Top Affiliating Genes
1 GTPase activator activity GO:0005096 9.13 SGSM1 OPHN1 ARHGAP42
2 protein domain specific binding GO:0019904 8.8 VRK2 CHMP1B CHMP1A

Sources for Pontocerebellar Hypoplasia, Type 1a

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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