PCH9
MCID: PNT032
MIFTS: 40

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 57 29 6 70
Pontocerebellar Hypoplasia Type 9 12 58 15
Pch9 57 58 72
Hypoplasia, Pontocerebellar, Type 9 39
Pontocerebellar Hypoplasia 9 72

Characteristics:

Orphanet epidemiological data:

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

OMIM®:

57 (Updated 05-Apr-2021)
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® 57 615809
OMIM Phenotypic Series 57 PS607596
MeSH 44 D002526
ICD10 32 Q04.3
ICD10 via Orphanet 33 Q04.3
Orphanet 58 ORPHA369920
UMLS 70 C4014354

Summaries for Pontocerebellar Hypoplasia, Type 9

OMIM® : 57 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) (Updated 05-Apr-2021)

MalaCards based summary : Pontocerebellar Hypoplasia, Type 9, also known as pontocerebellar hypoplasia type 9, is related to pontocerebellar hypoplasia and stickler syndrome, 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 spasticity and clonus

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 : 72 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 Pontocerebellar Hypoplasia Type 1

Diseases related to Pontocerebellar Hypoplasia, Type 9 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 16)
# Related Disease Score Top Affiliating Genes
1 pontocerebellar hypoplasia 30.1 VRK1 COL11A1 AMPD2
2 stickler syndrome 29.7 COL11A1 AMPD2
3 spastic paraplegia 63, autosomal recessive 10.2
4 paraplegia 10.2
5 corpus callosum, partial agenesis of, x-linked 10.1
6 astigmatism 10.1
7 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.1
8 sensorineural hearing loss 10.1
9 microcephaly 10.1
10 myopia 10.1
11 periventricular leukomalacia 10.1
12 hereditary spastic paraplegia 10.1
13 hypotonia 10.1
14 spasticity 10.1
15 anterior horn cell disease 9.9 VRK1 AMPD2
16 megalocornea 9.7 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 spasticity 31 HP:0001257
2 clonus 31 HP:0002169
3 macroglossia 31 HP:0000158
4 global developmental delay 31 HP:0001263
5 optic atrophy 31 HP:0000648
6 cerebral cortical atrophy 31 HP:0002120
7 downslanted palpebral fissures 31 HP:0000494
8 ventriculomegaly 31 HP:0002119
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 peripheral axonal neuropathy 31 HP:0003477
15 narrow forehead 31 HP:0000341
16 facial hypotonia 31 HP:0000297
17 progressive microcephaly 31 HP:0000253
18 short upper lip 31 HP:0000188
19 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
spasticity
hyperreflexia
clonus
cerebral cortical atrophy
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 (Updated 05-Apr-2021)

UMLS symptoms related to Pontocerebellar Hypoplasia, Type 9:


seizures; clonus; muscle spasticity

MGI Mouse Phenotypes related to Pontocerebellar Hypoplasia, Type 9:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 immune system MP:0005387 9.35 AMPD2 AMPD3 CLCA1 COL11A1 SH3PXD2B
2 nervous system MP:0003631 9.02 AMPD2 AMPD3 CLCA1 COL11A1 SH3PXD2B

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 14)
# Title Authors PMID Year
1
Complete callosal agenesis, pontocerebellar hypoplasia, and axonal neuropathy due to AMPD2 loss. 6 57
27066553 2015
2
AMPD2 regulates GTP synthesis and is mutated in a potentially treatable neurodegenerative brainstem disorder. 6 57
23911318 2013
3
First-line exome sequencing in Palestinian and Israeli Arabs with neurological disorders is efficient and facilitates disease gene discovery. 6
32214227 2020
4
Novel AMPD2 mutation in pontocerebellar hypoplasia, dysmorphisms, and teeth abnormalities. 6
28815207 2017
5
Homozygous variants in AMPD2 and COL11A1 lead to a complex phenotype of pontocerebellar hypoplasia type 9 and Stickler syndrome type 2. 61
31833174 2020
6
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
7
CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63. 61
30089829 2019
8
Clinical and genetic spectrum of AMPD2-related pontocerebellar hypoplasia type 9. 61
29463858 2018
9
Teaching NeuroImages: Figure of 8: The clue to the diagnosis of AMPD2 pontocerebellar hypoplasia (PCH9). 61
28972112 2017
10
A novel AMPD2 mutation outside the AMP deaminase domain causes pontocerebellar hypoplasia type 9. 61
28168832 2017
11
KNK437 Inhibits Replication and Transcription of the Hepatitis B Virus. 61
30702818 2017
12
Hsa-miR-331-3p inhibits VHL expression by directly targeting its mRNA 3'-UTR in HCC cell lines. 61
25750939 2015
13
[Regulation of microRNA-122 on HBV replication by targeting HBx sequence]. 61
21936381 2011
14
[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 49)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 AMPD2 NM_001368809.2(AMPD2):c.1492del (p.Asp498fs) Deletion Pathogenic 132809 rs587777391 GRCh37: 1:110171347-110171347
GRCh38: 1:109628725-109628725
2 AMPD2 NM_001368809.2(AMPD2):c.2172G>C (p.Glu724Asp) SNV Pathogenic 132810 rs587777392 GRCh37: 1:110173319-110173319
GRCh38: 1:109630697-109630697
3 AMPD2 NM_001368809.2(AMPD2):c.885C>A (p.Tyr295Ter) SNV Pathogenic 132811 rs587777393 GRCh37: 1:110170075-110170075
GRCh38: 1:109627453-109627453
4 AMPD2 NM_001368809.2(AMPD2):c.2215G>T (p.Asp739Tyr) SNV Pathogenic 132812 rs587777394 GRCh37: 1:110173362-110173362
GRCh38: 1:109630740-109630740
5 AMPD2 NM_001368809.2(AMPD2):c.2094C>G (p.Tyr698Ter) SNV Pathogenic 225763 rs875989844 GRCh37: 1:110172965-110172965
GRCh38: 1:109630343-109630343
6 AMPD2 NM_001257360.2:c.495delG Deletion Pathogenic 810627 GRCh37:
GRCh38:
7 AMPD2 NM_001368809.2(AMPD2):c.1198C>T (p.Gln400Ter) SNV Pathogenic 975089 GRCh37: 1:110170822-110170822
GRCh38: 1:109628200-109628200
8 AMPD2 NM_001368809.2(AMPD2):c.2165T>G (p.Leu722Arg) SNV Pathogenic 488467 rs1553230375 GRCh37: 1:110173312-110173312
GRCh38: 1:109630690-109630690
9 AMPD2 NM_001368809.2(AMPD2):c.4G>A (p.Ala2Thr) SNV Pathogenic 1027847 GRCh37: 1:110163801-110163801
GRCh38: 1:109621179-109621179
10 AMPD2 NM_001368809.2(AMPD2):c.274G>T (p.Glu92Ter) SNV Pathogenic 1033799 GRCh37: 1:110168335-110168335
GRCh38: 1:109625713-109625713
11 AMPD2 NM_001368809.2(AMPD2):c.1859G>A (p.Arg620His) SNV Likely pathogenic 132813 rs587777395 GRCh37: 1:110172109-110172109
GRCh38: 1:109629487-109629487
12 AMPD2 NM_001368809.2(AMPD2):c.1345C>T (p.Arg449Ter) SNV Likely pathogenic 813899 rs760433806 GRCh37: 1:110171055-110171055
GRCh38: 1:109628433-109628433
13 AMPD2 NM_001368809.2(AMPD2):c.1871G>T (p.Gly624Val) SNV Uncertain significance 972414 GRCh37: 1:110172426-110172426
GRCh38: 1:109629804-109629804
14 AMPD2 NM_001368809.2(AMPD2):c.175C>T (p.Leu59Phe) SNV Uncertain significance 1024841 GRCh37: 1:110168008-110168008
GRCh38: 1:109625386-109625386
15 AMPD2 NM_001368809.2(AMPD2):c.1522C>T (p.Arg508Cys) SNV Uncertain significance 939658 GRCh37: 1:110171379-110171379
GRCh38: 1:109628757-109628757
16 AMPD2 NM_001368809.2(AMPD2):c.288G>C (p.Glu96Asp) SNV Uncertain significance 951532 GRCh37: 1:110168349-110168349
GRCh38: 1:109625727-109625727
17 AMPD2 NM_001368809.2(AMPD2):c.2039C>T (p.Pro680Leu) SNV Uncertain significance 961257 GRCh37: 1:110172910-110172910
GRCh38: 1:109630288-109630288
18 AMPD2 NM_001368809.2(AMPD2):c.1072A>G (p.Ile358Val) SNV Uncertain significance 864592 GRCh37: 1:110170517-110170517
GRCh38: 1:109627895-109627895
19 AMPD2 NM_001368809.2(AMPD2):c.2327del (p.Ile776fs) Deletion Uncertain significance 975090 GRCh37: 1:110173623-110173623
GRCh38: 1:109631001-109631001
20 AMPD2 NM_001368809.2(AMPD2):c.428A>G (p.Tyr143Cys) SNV Uncertain significance 863422 GRCh37: 1:110168946-110168946
GRCh38: 1:109626324-109626324
21 AMPD2 NM_001368809.2(AMPD2):c.134G>A (p.Arg45Gln) SNV Uncertain significance 940457 GRCh37: 1:110167967-110167967
GRCh38: 1:109625345-109625345
22 AMPD2 NM_001368809.2(AMPD2):c.1778C>T (p.Ala593Val) SNV Uncertain significance 944582 GRCh37: 1:110172028-110172028
GRCh38: 1:109629406-109629406
23 AMPD2 NM_001368809.2(AMPD2):c.852CGA[1] (p.Asp285del) Microsatellite Uncertain significance 956565 GRCh37: 1:110169930-110169932
GRCh38: 1:109627308-109627310
24 AMPD2 NM_001368809.2(AMPD2):c.23C>G (p.Ser8Cys) SNV Uncertain significance 474995 rs147463318 GRCh37: 1:110163820-110163820
GRCh38: 1:109621198-109621198
25 AMPD2 NM_001368809.2(AMPD2):c.106C>G (p.Leu36Val) SNV Uncertain significance 474997 rs749918422 GRCh37: 1:110167939-110167939
GRCh38: 1:109625317-109625317
26 AMPD2 NM_001368809.2(AMPD2):c.971G>T (p.Arg324Leu) SNV Uncertain significance 571097 rs746332433 GRCh37: 1:110170416-110170416
GRCh38: 1:109627794-109627794
27 AMPD2 NM_001368809.2(AMPD2):c.1207C>T (p.Arg403Trp) SNV Uncertain significance 574248 rs373128067 GRCh37: 1:110170831-110170831
GRCh38: 1:109628209-109628209
28 AMPD2 NM_001368809.2(AMPD2):c.1192C>T (p.Arg398Cys) SNV Uncertain significance 578069 rs570605098 GRCh37: 1:110170816-110170816
GRCh38: 1:109628194-109628194
29 AMPD2 NM_001368809.2(AMPD2):c.806T>C (p.Leu269Pro) SNV Uncertain significance 638368 rs1570587910 GRCh37: 1:110169884-110169884
GRCh38: 1:109627262-109627262
30 AMPD2 NM_001368809.2(AMPD2):c.-75G>T SNV Uncertain significance 649488 rs1025210705 GRCh37: 1:110163723-110163723
GRCh38: 1:109621101-109621101
31 AMPD2 NM_001368809.2(AMPD2):c.178G>A (p.Asp60Asn) SNV Uncertain significance 655115 rs754712604 GRCh37: 1:110168011-110168011
GRCh38: 1:109625389-109625389
32 AMPD2 NM_001368809.2(AMPD2):c.1328T>C (p.Ile443Thr) SNV Uncertain significance 665782 rs149171366 GRCh37: 1:110171038-110171038
GRCh38: 1:109628416-109628416
33 AMPD2 NM_001368809.2(AMPD2):c.72G>A (p.Gln24=) SNV Likely benign 474996 rs143354905 GRCh37: 1:110163869-110163869
GRCh38: 1:109621247-109621247
34 AMPD2 NM_001368809.2(AMPD2):c.353+10G>A SNV Likely benign 541841 rs1269768577 GRCh37: 1:110168424-110168424
GRCh38: 1:109625802-109625802
35 AMPD2 NM_001368809.2(AMPD2):c.537G>A (p.Pro179=) SNV Likely benign 541842 rs776483432 GRCh37: 1:110169353-110169353
GRCh38: 1:109626731-109626731
36 AMPD2 NM_001368809.2(AMPD2):c.633C>G (p.Thr211=) SNV Likely benign 474998 rs141818976 GRCh37: 1:110169449-110169449
GRCh38: 1:109626827-109626827
37 AMPD2 NM_001368809.2(AMPD2):c.27C>A (p.Gly9=) SNV Likely benign 731965 rs141792341 GRCh37: 1:110163824-110163824
GRCh38: 1:109621202-109621202
38 AMPD2 NM_001368809.2(AMPD2):c.1992C>T (p.Val664=) SNV Likely benign 704805 rs143163487 GRCh37: 1:110172863-110172863
GRCh38: 1:109630241-109630241
39 AMPD2 NM_001368809.2(AMPD2):c.-112G>A SNV Likely benign 706538 rs759948714 GRCh37: 1:110163686-110163686
GRCh38: 1:109621064-109621064
40 AMPD2 NM_001368809.2(AMPD2):c.582C>T (p.Leu194=) SNV Likely benign 706575 rs144177097 GRCh37: 1:110169398-110169398
GRCh38: 1:109626776-109626776
41 AMPD2 NM_001368809.2(AMPD2):c.1407+3A>G SNV Likely benign 434144 rs41280332 GRCh37: 1:110171120-110171120
GRCh38: 1:109628498-109628498
42 AMPD2 NM_001368809.2(AMPD2):c.-52C>G SNV Benign 706956 rs570541266 GRCh37: 1:110163746-110163746
GRCh38: 1:109621124-109621124
43 AMPD2 NM_001368809.2(AMPD2):c.1242C>T (p.Tyr414=) SNV Benign 210136 rs114727970 GRCh37: 1:110170866-110170866
GRCh38: 1:109628244-109628244
44 AMPD2 NM_001368809.2(AMPD2):c.223-4C>T SNV Benign 210137 rs116223306 GRCh37: 1:110168280-110168280
GRCh38: 1:109625658-109625658
45 AMPD2 NM_001368809.2(AMPD2):c.1104G>A (p.Ser368=) SNV Benign 474994 rs34030799 GRCh37: 1:110170728-110170728
GRCh38: 1:109628106-109628106
46 AMPD2 NM_001368809.2(AMPD2):c.1587C>A (p.Thr529=) SNV Benign 703122 rs35337955 GRCh37: 1:110171746-110171746
GRCh38: 1:109629124-109629124
47 AMPD2 NM_001368809.2(AMPD2):c.708T>G (p.Pro236=) SNV Benign 703840 rs114624650 GRCh37: 1:110169524-110169524
GRCh38: 1:109626902-109626902
48 AMPD2 NM_001368809.2(AMPD2):c.1080+9T>C SNV Benign 703857 rs202160763 GRCh37: 1:110170534-110170534
GRCh38: 1:109627912-109627912
49 AMPD2 NM_001368809.2(AMPD2):c.1716C>T (p.Ser572=) SNV Benign 704004 rs116415979 GRCh37: 1:110171966-110171966
GRCh38: 1:109629344-109629344

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

72
# 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 nucleotide metabolic process GO:0009117 9.37 AMPD3 AMPD2
2 purine ribonucleoside monophosphate biosynthetic process GO:0009168 9.32 AMPD3 AMPD2
3 purine-containing compound salvage GO:0043101 9.26 AMPD3 AMPD2
4 AMP metabolic process GO:0046033 9.16 AMPD3 AMPD2
5 IMP salvage GO:0032264 8.96 AMPD3 AMPD2
6 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
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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