PCH9
MCID: PNT032
MIFTS: 41

Pontocerebellar Hypoplasia, Type 9 (PCH9)

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 9

MalaCards integrated aliases for Pontocerebellar Hypoplasia, Type 9:

Name: Pontocerebellar Hypoplasia, Type 9 56 29 6 71
Pontocerebellar Hypoplasia Type 9 12 58 15
Pch9 56 58 73
Hypoplasia, Pontocerebellar, Type 9 39
Pontocerebellar Hypoplasia 9 73

Characteristics:

Orphanet epidemiological data:

58
pontocerebellar hypoplasia type 9
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth or early infancy


HPO:

31
pontocerebellar hypoplasia, type 9:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0060278
OMIM 56 615809
OMIM Phenotypic Series 56 PS607596
MeSH 43 D002526
ICD10 32 Q04.3
ICD10 via Orphanet 33 Q04.3
Orphanet 58 ORPHA369920
UMLS 71 C4014354

Summaries for Pontocerebellar Hypoplasia, Type 9

OMIM : 56 Pontocerebellar hypoplasia type 9 is an autosomal recessive neurodevelopmental and neurodegenerative disorder characterized by severely delayed psychomotor development, progressive microcephaly, spasticity, seizures, and brain abnormalities, including brain atrophy, thin corpus callosum, and delayed myelination (summary by Akizu et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596). (615809)

MalaCards based summary : Pontocerebellar Hypoplasia, Type 9, also known as pontocerebellar hypoplasia type 9, is related to pontocerebellar hypoplasia and spastic paraplegia 63, autosomal recessive, and has symptoms including seizures, clonus and muscle spasticity. An important gene associated with Pontocerebellar Hypoplasia, Type 9 is AMPD2 (Adenosine Monophosphate Deaminase 2), and among its related pathways/superpathways is ATP/ITP metabolism. Affiliated tissues include brain, cerebellum and pons, and related phenotypes are macroglossia and global developmental delay

Disease Ontology : 12 A pontocerebellar hypoplasia that is characterized by progressive microcephaly, spasticity, seizure and brain atrophy, has material basis in autosomal recessive inheritance of mutation in the AMPD2 gene.

UniProtKB/Swiss-Prot : 73 Pontocerebellar hypoplasia 9: A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH9 features include severely delayed psychomotor development, progressive microcephaly, spasticity, seizures, and brain abnormalities, including brain atrophy, thin corpus callosum, and delayed myelination.

Related Diseases for Pontocerebellar Hypoplasia, Type 9

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 9 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 17)
# Related Disease Score Top Affiliating Genes
1 pontocerebellar hypoplasia 30.1 VRK1 AMPD2
2 spastic paraplegia 63, autosomal recessive 10.3
3 paraplegia 10.3
4 corpus callosum, partial agenesis of, x-linked 10.1
5 astigmatism 10.1
6 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.1
7 joint laxity, short stature, and myopia 10.1
8 stickler syndrome 10.1
9 sensorineural hearing loss 10.1
10 microcephaly 10.1
11 myopia 10.1
12 periventricular leukomalacia 10.1
13 hereditary spastic paraplegia 10.1
14 hypotonia 10.1
15 spasticity 10.1
16 anterior horn cell disease 9.5 VRK1 AMPD2
17 megalocornea 9.4 SH3PXD2B COL11A1

Graphical network of the top 20 diseases related to Pontocerebellar Hypoplasia, Type 9:



Diseases related to Pontocerebellar Hypoplasia, Type 9

Symptoms & Phenotypes for Pontocerebellar Hypoplasia, Type 9

Human phenotypes related to Pontocerebellar Hypoplasia, Type 9:

31 (show all 19)
# Description HPO Frequency HPO Source Accession
1 macroglossia 31 HP:0000158
2 global developmental delay 31 HP:0001263
3 optic atrophy 31 HP:0000648
4 spasticity 31 HP:0001257
5 cerebral cortical atrophy 31 HP:0002120
6 downslanted palpebral fissures 31 HP:0000494
7 ventriculomegaly 31 HP:0002119
8 clonus 31 HP:0002169
9 midface retrusion 31 HP:0011800
10 hypoplasia of the corpus callosum 31 HP:0002079
11 abnormality of the pinna 31 HP:0000377
12 muscular hypotonia of the trunk 31 HP:0008936
13 cerebral visual impairment 31 HP:0100704
14 narrow forehead 31 HP:0000341
15 facial hypotonia 31 HP:0000297
16 peripheral axonal neuropathy 31 HP:0003477
17 progressive microcephaly 31 HP:0000253
18 short upper lip 31 HP:0000188
19 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
seizures
spasticity
hyperreflexia
cerebral cortical atrophy
clonus
more
Head And Neck Head:
microcephaly, progressive (up to -9 sd)

Head And Neck Ears:
abnormally shaped ears (family a)

Neurologic Peripheral Nervous System:
axonal neuropathy (family a)

Head And Neck Eyes:
optic atrophy
cortical blindness
poor fixation
downslanting palpebral fissures (family a)

Head And Neck Face:
bitemporal narrowing (family a)
midface hypoplasia (family a)
hypotonic facies (family a)

Head And Neck Mouth:
short upper lip (family a)
macroglossia (family a)

Clinical features from OMIM:

615809

UMLS symptoms related to Pontocerebellar Hypoplasia, Type 9:


seizures, clonus, muscle spasticity

MGI Mouse Phenotypes related to Pontocerebellar Hypoplasia, Type 9:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 immune system MP:0005387 9.8 AMPD2 AMPD3 CLCA1 COL11A1 NF2 SH3PXD2B
2 mortality/aging MP:0010768 9.63 AMPD2 AMPD3 COL11A1 NF2 SH3PXD2B VRK1
3 nervous system MP:0003631 9.43 AMPD2 AMPD3 CLCA1 COL11A1 NF2 SH3PXD2B
4 respiratory system MP:0005388 8.92 AMPD3 CLCA1 COL11A1 NF2

Drugs & Therapeutics for Pontocerebellar Hypoplasia, Type 9

Search Clinical Trials , NIH Clinical Center for Pontocerebellar Hypoplasia, Type 9

Genetic Tests for Pontocerebellar Hypoplasia, Type 9

Genetic tests related to Pontocerebellar Hypoplasia, Type 9:

# Genetic test Affiliating Genes
1 Pontocerebellar Hypoplasia, Type 9 29 AMPD2

Anatomical Context for Pontocerebellar Hypoplasia, Type 9

MalaCards organs/tissues related to Pontocerebellar Hypoplasia, Type 9:

40
Brain, Cerebellum, Pons

Publications for Pontocerebellar Hypoplasia, Type 9

Articles related to Pontocerebellar Hypoplasia, Type 9:

(show all 12)
# Title Authors PMID Year
1
Complete callosal agenesis, pontocerebellar hypoplasia, and axonal neuropathy due to AMPD2 loss. 6 56
27066553 2015
2
AMPD2 regulates GTP synthesis and is mutated in a potentially treatable neurodegenerative brainstem disorder. 56 6
23911318 2013
3
Homozygous variants in AMPD2 and COL11A1 lead to a complex phenotype of pontocerebellar hypoplasia type 9 and Stickler syndrome type 2. 61
31833174 2020
4
Neuroradiological findings in three cases of pontocerebellar hypoplasia type 9 due to AMPD2 mutation: typical MRI appearances and pearls for differential diagnosis. 61
31929969 2019
5
CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63. 61
30089829 2019
6
Clinical and genetic spectrum of AMPD2-related pontocerebellar hypoplasia type 9. 61
29463858 2018
7
Teaching NeuroImages: Figure of 8: The clue to the diagnosis of AMPD2 pontocerebellar hypoplasia (PCH9). 61
28972112 2017
8
A novel AMPD2 mutation outside the AMP deaminase domain causes pontocerebellar hypoplasia type 9. 61
28168832 2017
9
KNK437 Inhibits Replication and Transcription of the Hepatitis B Virus. 61
30702818 2017
10
Hsa-miR-331-3p inhibits VHL expression by directly targeting its mRNA 3'-UTR in HCC cell lines. 61
25750939 2015
11
[Regulation of microRNA-122 on HBV replication by targeting HBx sequence]. 61
21936381 2011
12
[Down-regulation of hepatitis B virus replication by heparin sulfate-D-glucosaminyl-3-O-sulfotransferase 3B1]. 61
22053370 2011

Variations for Pontocerebellar Hypoplasia, Type 9

ClinVar genetic disease variations for Pontocerebellar Hypoplasia, Type 9:

6 (show all 37) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 AMPD2 NM_001368809.2(AMPD2):c.2165T>G (p.Leu722Arg)SNV Pathogenic 488467 rs1553230375 1:110173312-110173312 1:109630690-109630690
2 AMPD2 NM_001257360.2:c.495delGdeletion Pathogenic 810627
3 AMPD2 NM_001368809.2(AMPD2):c.1492del (p.Asp498fs)deletion Pathogenic 132809 rs587777391 1:110171347-110171347 1:109628725-109628725
4 AMPD2 NM_001368809.2(AMPD2):c.2172G>C (p.Glu724Asp)SNV Pathogenic 132810 rs587777392 1:110173319-110173319 1:109630697-109630697
5 AMPD2 NM_001368809.2(AMPD2):c.885C>A (p.Tyr295Ter)SNV Pathogenic 132811 rs587777393 1:110170075-110170075 1:109627453-109627453
6 AMPD2 NM_001368809.2(AMPD2):c.2215G>T (p.Asp739Tyr)SNV Pathogenic 132812 rs587777394 1:110173362-110173362 1:109630740-109630740
7 AMPD2 NM_001368809.2(AMPD2):c.1859G>A (p.Arg620His)SNV Pathogenic 132813 rs587777395 1:110172109-110172109 1:109629487-109629487
8 AMPD2 NM_001368809.2(AMPD2):c.2094C>G (p.Tyr698Ter)SNV Pathogenic 225763 rs875989844 1:110172965-110172965 1:109630343-109630343
9 AMPD2 NM_001368809.2(AMPD2):c.1345C>T (p.Arg449Ter)SNV Likely pathogenic 813899 1:110171055-110171055 1:109628433-109628433
10 AMPD2 NM_001368809.2(AMPD2):c.1242C>T (p.Tyr414=)SNV Conflicting interpretations of pathogenicity 210136 rs114727970 1:110170866-110170866 1:109628244-109628244
11 AMPD2 NM_001368809.2(AMPD2):c.1407+3A>GSNV Conflicting interpretations of pathogenicity 434144 rs41280332 1:110171120-110171120 1:109628498-109628498
12 AMPD2 NM_001368809.2(AMPD2):c.23C>G (p.Ser8Cys)SNV Uncertain significance 474995 rs147463318 1:110163820-110163820 1:109621198-109621198
13 AMPD2 NM_001368809.2(AMPD2):c.106C>G (p.Leu36Val)SNV Uncertain significance 474997 rs749918422 1:110167939-110167939 1:109625317-109625317
14 AMPD2 NM_001368809.2(AMPD2):c.971G>T (p.Arg324Leu)SNV Uncertain significance 571097 rs746332433 1:110170416-110170416 1:109627794-109627794
15 AMPD2 NM_001368809.2(AMPD2):c.1207C>T (p.Arg403Trp)SNV Uncertain significance 574248 rs373128067 1:110170831-110170831 1:109628209-109628209
16 AMPD2 NM_001368809.2(AMPD2):c.1192C>T (p.Arg398Cys)SNV Uncertain significance 578069 rs570605098 1:110170816-110170816 1:109628194-109628194
17 AMPD2 NM_001368809.2(AMPD2):c.806T>C (p.Leu269Pro)SNV Uncertain significance 638368 1:110169884-110169884 1:109627262-109627262
18 AMPD2 NM_001368809.2(AMPD2):c.-75G>TSNV Uncertain significance 649488 1:110163723-110163723 1:109621101-109621101
19 AMPD2 NM_001368809.2(AMPD2):c.178G>A (p.Asp60Asn)SNV Uncertain significance 655115 1:110168011-110168011 1:109625389-109625389
20 AMPD2 NM_001368809.2(AMPD2):c.1328T>C (p.Ile443Thr)SNV Uncertain significance 665782 1:110171038-110171038 1:109628416-109628416
21 AMPD2 NM_001368809.2(AMPD2):c.428A>G (p.Tyr143Cys)SNV Uncertain significance 863422 1:110168946-110168946 1:109626324-109626324
22 AMPD2 NM_001368809.2(AMPD2):c.1072A>G (p.Ile358Val)SNV Uncertain significance 864592 1:110170517-110170517 1:109627895-109627895
23 AMPD2 NM_001368809.2(AMPD2):c.582C>T (p.Leu194=)SNV Likely benign 706575 1:110169398-110169398 1:109626776-109626776
24 AMPD2 NM_001368809.2(AMPD2):c.27C>A (p.Gly9=)SNV Likely benign 731965 1:110163824-110163824 1:109621202-109621202
25 AMPD2 NM_001368809.2(AMPD2):c.1992C>T (p.Val664=)SNV Likely benign 704805 1:110172863-110172863 1:109630241-109630241
26 AMPD2 NM_001368809.2(AMPD2):c.-112G>ASNV Likely benign 706538 1:110163686-110163686 1:109621064-109621064
27 AMPD2 NM_001368809.2(AMPD2):c.353+10G>ASNV Likely benign 541841 rs1269768577 1:110168424-110168424 1:109625802-109625802
28 AMPD2 NM_001368809.2(AMPD2):c.537G>A (p.Pro179=)SNV Likely benign 541842 rs776483432 1:110169353-110169353 1:109626731-109626731
29 AMPD2 NM_001368809.2(AMPD2):c.633C>G (p.Thr211=)SNV Likely benign 474998 rs141818976 1:110169449-110169449 1:109626827-109626827
30 AMPD2 NM_001368809.2(AMPD2):c.72G>A (p.Gln24=)SNV Likely benign 474996 rs143354905 1:110163869-110163869 1:109621247-109621247
31 AMPD2 NM_001368809.2(AMPD2):c.223-4C>TSNV Benign/Likely benign 210137 rs116223306 1:110168280-110168280 1:109625658-109625658
32 AMPD2 NM_001368809.2(AMPD2):c.1080+9T>CSNV Benign 703857 1:110170534-110170534 1:109627912-109627912
33 AMPD2 NM_001368809.2(AMPD2):c.708T>G (p.Pro236=)SNV Benign 703840 1:110169524-110169524 1:109626902-109626902
34 AMPD2 NM_001368809.2(AMPD2):c.1587C>A (p.Thr529=)SNV Benign 703122 1:110171746-110171746 1:109629124-109629124
35 AMPD2 NM_001368809.2(AMPD2):c.1716C>T (p.Ser572=)SNV Benign 704004 1:110171966-110171966 1:109629344-109629344
36 AMPD2 NM_001368809.2(AMPD2):c.1104G>A (p.Ser368=)SNV Benign 474994 rs34030799 1:110170728-110170728 1:109628106-109628106
37 AMPD2 NM_001368809.2(AMPD2):c.-52C>GSNV Benign 706956 1:110163746-110163746 1:109621124-109621124

UniProtKB/Swiss-Prot genetic disease variations for Pontocerebellar Hypoplasia, Type 9:

73
# Symbol AA change Variation ID SNP ID
1 AMPD2 p.Arg674His VAR_071158 rs587777395
2 AMPD2 p.Asp793Tyr VAR_071159 rs587777394
3 AMPD2 p.Glu778Asp VAR_071193 rs587777392

Expression for Pontocerebellar Hypoplasia, Type 9

Search GEO for disease gene expression data for Pontocerebellar Hypoplasia, Type 9.

Pathways for Pontocerebellar Hypoplasia, Type 9

Pathways related to Pontocerebellar Hypoplasia, Type 9 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.55 AMPD3 AMPD2

GO Terms for Pontocerebellar Hypoplasia, Type 9

Biological processes related to Pontocerebellar Hypoplasia, Type 9 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of stress fiber assembly GO:0051496 9.46 SH3PXD2B NF2
2 skeletal system morphogenesis GO:0048705 9.43 SH3PXD2B COL11A1
3 energy homeostasis GO:0097009 9.4 AMPD3 AMPD2
4 nucleotide metabolic process GO:0009117 9.37 AMPD3 AMPD2
5 purine ribonucleoside monophosphate biosynthetic process GO:0009168 9.32 AMPD3 AMPD2
6 purine-containing compound salvage GO:0043101 9.26 AMPD3 AMPD2
7 AMP metabolic process GO:0046033 9.16 AMPD3 AMPD2
8 IMP salvage GO:0032264 8.96 AMPD3 AMPD2
9 IMP biosynthetic process GO:0006188 8.62 AMPD3 AMPD2

Molecular functions related to Pontocerebellar Hypoplasia, Type 9 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 deaminase activity GO:0019239 8.96 AMPD3 AMPD2
2 AMP deaminase activity GO:0003876 8.62 AMPD3 AMPD2

Sources for Pontocerebellar Hypoplasia, Type 9

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
Content
Loading form....