PCH2A
MCID: PNT044
MIFTS: 41

Pontocerebellar Hypoplasia, Type 2a (PCH2A)

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 2a

MalaCards integrated aliases for Pontocerebellar Hypoplasia, Type 2a:

Name: Pontocerebellar Hypoplasia, Type 2a 56
Pontocerebellar Hypoplasia Type 2a 56 12 29 13 6 43 15 71
Pontocerebellar Hypoplasia with Progressive Cerebral Atrophy 56 73
Volendam Neurodegenerative Disease 56 73
Pch2a 56 73
Pch2 56 73
Hypoplasia, Pontocerebellar, Type 2a 39
Pontocerebellar Hypoplasia 2a 73

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth
death in childhood may occur


HPO:

31
pontocerebellar hypoplasia, type 2a:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset
Clinical modifier death in childhood


Classifications:



External Ids:

Disease Ontology 12 DOID:0060267
OMIM 56 277470
OMIM Phenotypic Series 56 PS607596
MedGen 41 C1848526
UMLS 71 C1848526

Summaries for Pontocerebellar Hypoplasia, Type 2a

OMIM : 56 Pontocerebellar hypoplasia (PCH) represents a heterogeneous group of disorders characterized by an abnormally small cerebellum and brainstem. PCH type 2 is characterized by progressive microcephaly from birth combined with extrapyramidal dyskinesia and chorea, epilepsy, and normal spinal cord findings (Barth, 1993). For a phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596). (277470)

MalaCards based summary : Pontocerebellar Hypoplasia, Type 2a, also known as pontocerebellar hypoplasia type 2a, is related to pontocerebellar hypoplasia, type 2e and pontocerebellar hypoplasia, type 2d, and has symptoms including seizures, opisthotonus and muscle spasticity. An important gene associated with Pontocerebellar Hypoplasia, Type 2a is TSEN54 (TRNA Splicing Endonuclease Subunit 54), and among its related pathways/superpathways are tRNA processing and Transcription of tRNA. Affiliated tissues include cerebellum, spinal cord and cortex, and related phenotypes are cerebral cortical atrophy and microcephaly

Disease Ontology : 12 A severe pontocerebellar hypoplasia that is characterized by progressive microcephaly, chorea, epilepsy and hyperreflexia, has material basis in autosomal recessive inheritance of mutation in the TSEN54 gene.

UniProtKB/Swiss-Prot : 73 Pontocerebellar hypoplasia 2A: A disorder characterized by an abnormally small cerebellum and brainstem, and progressive microcephaly from birth combined with extrapyramidal dyskinesia. Severe chorea occurs and epilepsy is frequent. There are no signs of spinal cord anterior horn cells degeneration.

Related Diseases for Pontocerebellar Hypoplasia, Type 2a

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
Pontocerebellar Hypoplasia Type 1

Diseases related to Pontocerebellar Hypoplasia, Type 2a via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 27)
# Related Disease Score Top Affiliating Genes
1 pontocerebellar hypoplasia, type 2e 32.5 TSEN54 TSEN34 TSEN2 SEPSECS
2 pontocerebellar hypoplasia, type 2d 32.0 TSEN54 SEPSECS
3 tsen54 pontocerebellar hypoplasia 30.5 TSEN54 TSEN34 TSEN2
4 pontocerebellar hypoplasia 29.5 TSEN54 TSEN34 TSEN2 TRIP13 SEPSECS
5 pontocerebellar hypoplasia, type 2f 11.2
6 pontocerebellar hypoplasia, type 5 10.2 TSEN54 TRIP13
7 colon adenocarcinoma 10.2
8 breast adenocarcinoma 10.2
9 pontocerebellar hypoplasia type 1 10.2
10 hypertonia 10.2
11 thyroid carcinoma 10.2
12 gastroesophageal reflux 10.2
13 microcephaly 10.2
14 status epilepticus 10.2
15 sleep disorder 10.2
16 spasticity 10.2
17 pontocerebellar hypoplasia, type 6 10.1 TSEN54 TSEN34 TSEN2
18 peho syndrome 10.1 TSEN54 TSEN34 TSEN2
19 pontocerebellar hypoplasia, type 4 10.1 TSEN54 TRIP13
20 hemoglobin h disease 10.1 TSEN54 TSEN34 TSEN2
21 polyhydramnios 10.1 TSEN54 TSEN34 TSEN2
22 mental retardation and microcephaly with pontine and cerebellar hypoplasia 10.0 TSEN54 TRIP13
23 dyskinetic cerebral palsy 10.0 TSEN54 JRK
24 cardiomyopathy, familial restrictive, 1 9.9 NSUN2 FTSJ1
25 smoldering myeloma 9.8 MAF B2M
26 autoimmune atherosclerosis 9.8 HSPD1 HSPA14
27 thiamine-responsive megaloblastic anemia syndrome 9.8 NSUN2 FTSJ1

Graphical network of the top 20 diseases related to Pontocerebellar Hypoplasia, Type 2a:



Diseases related to Pontocerebellar Hypoplasia, Type 2a

Symptoms & Phenotypes for Pontocerebellar Hypoplasia, Type 2a

Human phenotypes related to Pontocerebellar Hypoplasia, Type 2a:

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 cerebral cortical atrophy 31 occasional (7.5%) HP:0002120
2 microcephaly 31 HP:0000252
3 visual impairment 31 HP:0000505
4 feeding difficulties in infancy 31 HP:0008872
5 severe global developmental delay 31 HP:0011344
6 cerebellar hypoplasia 31 HP:0001321
7 restlessness 31 HP:0000711
8 poor suck 31 HP:0002033
9 abnormality of the periventricular white matter 31 HP:0002518
10 hypoplasia of the pons 31 HP:0012110
11 impaired smooth pursuit 31 HP:0007772
12 opisthotonus 31 HP:0002179
13 gliosis 31 HP:0002171
14 progressive microcephaly 31 HP:0000253
15 extrapyramidal dyskinesia 31 HP:0007308
16 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
seizures
spasticity
opisthotonus
extrapyramidal dyskinesia
cerebellar cortex shows normal layers
more
Head And Neck Head:
microcephaly, progressive

Head And Neck Eyes:
central visual impairment
abnormal visual pursuit

Abdomen Gastrointestinal:
poor feeding
poor sucking

Muscle Soft Tissue:
hypertonia at birth

Clinical features from OMIM:

277470

UMLS symptoms related to Pontocerebellar Hypoplasia, Type 2a:


seizures, opisthotonus, muscle spasticity

Drugs & Therapeutics for Pontocerebellar Hypoplasia, Type 2a

Search Clinical Trials , NIH Clinical Center for Pontocerebellar Hypoplasia, Type 2a

Cochrane evidence based reviews: pontocerebellar hypoplasia type 2a

Genetic Tests for Pontocerebellar Hypoplasia, Type 2a

Genetic tests related to Pontocerebellar Hypoplasia, Type 2a:

# Genetic test Affiliating Genes
1 Pontocerebellar Hypoplasia Type 2a 29 TSEN54

Anatomical Context for Pontocerebellar Hypoplasia, Type 2a

MalaCards organs/tissues related to Pontocerebellar Hypoplasia, Type 2a:

40
Cerebellum, Spinal Cord, Cortex, Pons

Publications for Pontocerebellar Hypoplasia, Type 2a

Articles related to Pontocerebellar Hypoplasia, Type 2a:

(show all 11)
# Title Authors PMID Year
1
Pontocerebellar hypoplasia: clinical, pathologic, and genetic studies. 56 6
20956791 2010
2
tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia. 56 6
18711368 2008
3
TSEN54 mutations cause pontocerebellar hypoplasia type 5. 6
21368912 2011
4
Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. 56
20952379 2011
5
Molecular and neuroimaging findings in pontocerebellar hypoplasia type 2 (PCH2): is prenatal diagnosis possible? 56
20803644 2010
6
TSEN54 Pontocerebellar Hypoplasia 6
20301773 2009
7
The syndrome of autosomal recessive pontocerebellar hypoplasia, microcephaly, and extrapyramidal dyskinesia (pontocerebellar hypoplasia type 2): compiled data from 10 pedigrees. 56
7854532 1995
8
Pontocerebellar hypoplasias. An overview of a group of inherited neurodegenerative disorders with fetal onset. 56
8147499 1993
9
Inherited syndrome of microcephaly, dyskinesia and pontocerebellar hypoplasia: a systemic atrophy with early onset. 56
2370559 1990
10
Cerebellar hypoplasia associated with systemic degeneration in early life. 56
13576165 1958
11
Natural course of pontocerebellar hypoplasia type 2A. 61
24886362 2014

Variations for Pontocerebellar Hypoplasia, Type 2a

ClinVar genetic disease variations for Pontocerebellar Hypoplasia, Type 2a:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TSEN54 NM_207346.3(TSEN54):c.940del (p.Leu314fs)deletion Pathogenic 561138 rs1012275384 17:73518100-73518100 17:75522019-75522019
2 TSEN54 NM_207346.3(TSEN54):c.1397dup (p.Gly467fs)duplication Pathogenic 212452 rs797046055 17:73519824-73519825 17:75523743-75523744
3 TSEN54 NM_207346.3(TSEN54):c.823del (p.Val275fs)deletion Pathogenic 212454 rs797046057 17:73517981-73517981 17:75521900-75521900
4 TSEN54 NM_207346.3(TSEN54):c.1386_1387insTA (p.Lys463Ter)insertion Pathogenic 212451 rs797046054 17:73519815-73519816 17:75523734-75523735
5 TSEN54 NM_207346.3(TSEN54):c.919G>T (p.Ala307Ser)SNV Pathogenic/Likely pathogenic 2120 rs113994152 17:73518081-73518081 17:75522000-75522000
6 TSEN54 NM_207346.3(TSEN54):c.1535T>C (p.Phe512Ser)SNV Likely pathogenic 638161 17:73520447-73520447 17:75524366-75524366
7 TSEN54 NM_207346.3(TSEN54):c.371G>T (p.Gly124Val)SNV Likely pathogenic 495240 rs774157225 17:73513639-73513639 17:75517558-75517558
8 TSEN54 NM_207346.3(TSEN54):c.277T>C (p.Ser93Pro)SNV Uncertain significance 38455 rs113994151 17:73513145-73513145 17:75517064-75517064
9 TSEN54 NM_207346.3(TSEN54):c.622C>T (p.Arg208Trp)SNV Uncertain significance 198637 rs147165460 17:73517590-73517590 17:75521509-75521509
10 TSEN54 NM_207346.3(TSEN54):c.83C>T (p.Ser28Leu)SNV Uncertain significance 212455 rs201089582 17:73512853-73512853 17:75516772-75516772

UniProtKB/Swiss-Prot genetic disease variations for Pontocerebellar Hypoplasia, Type 2a:

73
# Symbol AA change Variation ID SNP ID
1 TSEN54 p.Ala307Ser VAR_054813 rs113994152
2 TSEN54 p.Tyr119Asp VAR_073351

Expression for Pontocerebellar Hypoplasia, Type 2a

Search GEO for disease gene expression data for Pontocerebellar Hypoplasia, Type 2a.

Pathways for Pontocerebellar Hypoplasia, Type 2a

Pathways related to Pontocerebellar Hypoplasia, Type 2a according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.39 TSEN54 TSEN34 TSEN2 NSUN2 FTSJ1
2
Show member pathways
10.73 TSEN54 TSEN34 TSEN2
3 10.43 VCPKMT METTL21A

GO Terms for Pontocerebellar Hypoplasia, Type 2a

Cellular components related to Pontocerebellar Hypoplasia, Type 2a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 9.73 UBE2O TSEN54 TSEN34 TSEN2 TRIP13 SEPSECS
2 tRNA-intron endonuclease complex GO:0000214 8.8 TSEN54 TSEN34 TSEN2

Biological processes related to Pontocerebellar Hypoplasia, Type 2a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 tRNA processing GO:0008033 9.55 TSEN54 TSEN34 TSEN2 NSUN2 FTSJ1
2 protein refolding GO:0042026 9.5 HSPD1 HSPA14 B2M
3 tRNA methylation GO:0030488 9.48 NSUN2 FTSJ1
4 tRNA modification GO:0006400 9.46 NSUN2 FTSJ1
5 protein methylation GO:0006479 9.43 VCPKMT METTL21A
6 tRNA splicing, via endonucleolytic cleavage and ligation GO:0006388 9.43 TSEN54 TSEN34 TSEN2
7 methylation GO:0032259 9.43 VCPKMT NSUN2 METTL23 METTL21A FTSJ1 EHMT1
8 RNA methylation GO:0001510 9.4 NSUN2 FTSJ1
9 peptidyl-lysine methylation GO:0018022 9.37 VCPKMT METTL21A
10 tRNA-type intron splice site recognition and cleavage GO:0000379 8.8 TSEN54 TSEN34 TSEN2

Molecular functions related to Pontocerebellar Hypoplasia, Type 2a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity GO:0016740 9.92 VCPKMT UBE2O SEPSECS NSUN2 METTL23 METTL21A
2 heat shock protein binding GO:0031072 9.43 METTL23 METTL21A HSPA14
3 tRNA-intron endonuclease activity GO:0000213 9.16 TSEN34 TSEN2
4 protein-lysine N-methyltransferase activity GO:0016279 9.13 VCPKMT METTL21A EHMT1
5 methyltransferase activity GO:0008168 9.1 VCPKMT NSUN2 METTL23 METTL21A FTSJ1 EHMT1

Sources for Pontocerebellar Hypoplasia, Type 2a

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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