Details of Disease

General Information of Disease (ID: DISRICMU)

Disease Name Pontocerebellar hypoplasia
Synonyms isolated pontocerebellar hypoplasia; nonsyndromic pontocerebellar hypoplasia; PCH; pontoneocerebellar atrophy; pontocerebellar hypoplasia; pontoneocerebllar hypoplasia
Definition
Pontocerebellar hypoplasias (PCH) are a rare heterogeneous group of diseases characterized by hypoplasia and atrophy and/or early neurodegeneration of the cerebellum and pons. Eight subtypes named type 1-8 have been described, generally inherited in an autosomal recessive pattern.
Disease Hierarchy
DISD715V: Hereditary neurological disease
DISOV08L: Central nervous system malformation
DISRICMU: Pontocerebellar hypoplasia
Disease Identifiers
MONDO ID
MONDO_0020135
UMLS CUI
C1261175
MedGen ID
224703
Orphanet ID
98523

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)
This Disease Is Related to 2 DTT Molecule(s)
Gene Name DTT ID Evidence Level Mode of Inheritance REF
COASY TT4YO0Z Strong Genetic Variation [1]
KIF26B TTQWICZ Strong Biomarker [2]
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This Disease Is Related to 15 DOT Molecule(s)
Gene Name DOT ID Evidence Level Mode of Inheritance REF
AMPD2 OTBS30JU Strong Genetic Variation [3]
CHMP1A OTVQ5UWX Strong Genetic Variation [4]
DKC1 OTX7DJR6 Strong Genetic Variation [5]
EXOSC3 OTNCF906 Strong Biomarker [6]
EXOSC8 OT75ACNG Strong Genetic Variation [7]
PCLO OTXJZZ98 Strong Biomarker [8]
RARS2 OT3WLAD8 Strong Biomarker [9]
RBM7 OTFIWTMF Strong Biomarker [10]
SLC25A46 OTFEV9SV Strong Genetic Variation [11]
TBC1D23 OTJMGQNZ Strong Genetic Variation [12]
TOE1 OTVWYJS9 Strong Genetic Variation [13]
TRIP13 OTFM3TI9 Strong Genetic Variation [14]
TSEN15 OT14UW31 Strong Biomarker [14]
TSEN34 OTH5FQHP Strong Genetic Variation [15]
CASK OT8EF7ZF Definitive Genetic Variation [16]
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⏷ Show the Full List of 15 DOT(s)

References

1 Biallelic loss of function variants in COASY cause prenatal onset pontocerebellar hypoplasia, microcephaly, and arthrogryposis. Eur J Hum Genet. 2018 Dec;26(12):1752-1758. doi: 10.1038/s41431-018-0233-0. Epub 2018 Aug 8.
2 De novo variant in KIF26B is associated with pontocerebellar hypoplasia with infantile spinal muscular atrophy.Am J Med Genet A. 2018 Dec;176(12):2623-2629. doi: 10.1002/ajmg.a.40493. Epub 2018 Aug 27.
3 Clinical and genetic spectrum of AMPD2-related pontocerebellar hypoplasia type 9.Eur J Hum Genet. 2018 May;26(5):695-708. doi: 10.1038/s41431-018-0098-2. Epub 2018 Feb 20.
4 The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles.Cell Rep. 2018 Jul 24;24(4):973-986.e8. doi: 10.1016/j.celrep.2018.06.100.
5 Novel Mutation in the DKC1 Gene: Neonatal Hoyeraal-Hreidarsson Syndrome As a Rare Differential Diagnosis in Pontocerebellar Hypoplasia, Primary Microcephaly, and Progressive Bone Marrow Failure.Neuropediatrics. 2016 Jun;47(3):182-6. doi: 10.1055/s-0036-1578799. Epub 2016 Mar 7.
6 Sarcomeric disorganization and nemaline bodies in muscle biopsies of patients with EXOSC3-related type 1 pontocerebellar hypoplasia.Muscle Nerve. 2019 Jan;59(1):137-141. doi: 10.1002/mus.26305. Epub 2018 Dec 16.
7 Altered RNA metabolism due to a homozygous RBM7 mutation in a patient with spinal motor neuropathy.Hum Mol Genet. 2016 Jul 15;25(14):2985-2996. doi: 10.1093/hmg/ddw149. Epub 2016 May 18.
8 Loss of PCLO function underlies pontocerebellar hypoplasia type III. Neurology. 2015 Apr 28;84(17):1745-50. doi: 10.1212/WNL.0000000000001523. Epub 2015 Apr 1.
9 RARS2 mutations in a sibship with infantile spasms.Epilepsia. 2016 May;57(5):e97-e102. doi: 10.1111/epi.13358. Epub 2016 Apr 8.
10 Variants in EXOSC9 Disrupt the RNA Exosome and Result in Cerebellar Atrophy with Spinal Motor Neuronopathy. Am J Hum Genet. 2018 May 3;102(5):858-873. doi: 10.1016/j.ajhg.2018.03.011.
11 Extension of the phenotype of biallelic loss-of-function mutations in SLC25A46 to the severe form of pontocerebellar hypoplasia type I.Clin Genet. 2018 Feb;93(2):255-265. doi: 10.1111/cge.13084. Epub 2017 Nov 8.
12 Structural and functional studies of TBC1D23 C-terminal domain provide a link between endosomal trafficking and PCH.Proc Natl Acad Sci U S A. 2019 Nov 5;116(45):22598-22608. doi: 10.1073/pnas.1909316116. Epub 2019 Oct 17.
13 Biallelic mutations in the 3' exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing. Nat Genet. 2017 Mar;49(3):457-464. doi: 10.1038/ng.3762. Epub 2017 Jan 16.
14 Autosomal-Recessive Mutations in the tRNA Splicing Endonuclease Subunit TSEN15 Cause Pontocerebellar Hypoplasia and Progressive Microcephaly. Am J Hum Genet. 2016 Jul 7;99(1):228-35. doi: 10.1016/j.ajhg.2016.05.023.
15 Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia.Brain. 2011 Jan;134(Pt 1):143-56. doi: 10.1093/brain/awq287. Epub 2010 Oct 15.
16 Novel CASK mutations in cases with syndromic microcephaly.Hum Mutat. 2018 Jul;39(7):993-1001. doi: 10.1002/humu.23536. Epub 2018 May 11.