KEGG   DISEASE: Pontocerebellar hypoplasiaHelp
Entry
H00897                      Disease                                

Name
Pontocerebellar hypoplasia
Description
Pontocerebellar hypoplasia (PCH) is a group of inherited progressive neurodegenerative disorders with prenatal onset. Up to now ten different subtypes have been reported. All subtypes share common characteristics, including hypoplasia/atrophy of cerebellum and pons, progressive microcephaly, and variable cerebral involvement. Mutations in three tRNA splicing endonuclease subunit genes were found to be responsible for PCH2, PCH4 and PCH5. Mutations in the nuclear encoded mitochondrial arginyl- tRNA synthetase gene underlie PCH6. PCH1 is caused by homozygous mutation in the VRK1 gene.
Category
Neurodegenerative disease; Developmental disorder
Brite
Human diseases [BR:br08402]
 Nervous system diseases
  Neurodegenerative diseases
   H00897  Pontocerebellar hypoplasia
Human diseases in ICD-11 classification [BR:br08403]
 20 Developmental anomalies
  Multiple developmental anomalies or syndromes
   LD20  Syndromes with central nervous system anomalies as a major feature
    H00897  Pontocerebellar hypoplasia
BRITE hierarchy
Pathway
hsa00970  Aminoacyl-tRNA biosynthesis
hsa03015  mRNA surveillance pathway
hsa03018  RNA degradation
Gene
(PCH1) VRK1 [HSA:7443] [KO:K08816]
(PCH1B) EXOSC3 [HSA:51010] [KO:K03681]
(PCH1C) EXOSC8 [HSA:11340] [KO:K12586]
(PCH2A/4/5) TSEN54 [HSA:283989] [KO:K15326]
(PCH2B) TSEN2 [HSA:80746] [KO:K15322]
(PCH2C) TSEN34 [HSA:79042] [KO:K15323]
(PCH2D) SEPSECS [HSA:51091] [KO:K03341]
(PCH2E) VPS53 [HSA:55275] [KO:K20299]
(PCH2F) TSEN15 [HSA:116461] [KO:K15324]
(PCH3) PCLO [HSA:27445] [KO:K16882]
(PCH6) RARS2 [HSA:57038] [KO:K01887]
(PCH7) TOE1 [HSA:114034] [KO:K13202]
(PCH8) CHMP1A [HSA:5119] [KO:K12197]
(PCH9) AMPD2 [HSA:271] [KO:K01490]
(PCH10) CLP1 [HSA:10978] [KO:K14399]
Other DBs
ICD-11: LD20.01
ICD-10: Q04.3
MeSH: C580383
OMIM: 607596 614678 616081 277470 225753 612389 612390 611523 608027 613811 615851 617026 614969 614961 615809 615803
Reference
  Authors
Namavar Y, Barth PG, Poll-The BT, Baas F
  Title
Classification, diagnosis and potential mechanisms in pontocerebellar hypoplasia.
  Journal
Orphanet J Rare Dis 6:50 (2011)
DOI:10.1186/1750-1172-6-50
Reference
  Authors
Biancheri R, Cassandrini D, Pinto F, Trovato R, Di Rocco M, Mirabelli-Badenier M, Pedemonte M, Panicucci C, Trucks H, Sander T, Zara F, Rossi A, Striano P, Minetti C, Santorelli FM
  Title
EXOSC3 mutations in isolated cerebellar hypoplasia and spinal anterior horn involvement.
  Journal
J Neurol 260:1866-70 (2013)
DOI:10.1007/s00415-013-6896-0
Reference
  Authors
Boczonadi V, Muller JS, Pyle A, Munkley J, Dor T, Quartararo J, Ferrero I, Karcagi V, Giunta M, Polvikoski T, Birchall D, Princzinger A, Cinnamon Y, Lutzkendorf S, Piko H, Reza M, Florez L, Santibanez-Koref M, Griffin H, Schuelke M, Elpeleg O, Kalaydjieva L, Lochmuller H, Elliott DJ, Chinnery PF, Edvardson S, Horvath R
  Title
EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia.
  Journal
Nat Commun 5:4287 (2014)
DOI:10.1038/ncomms5287
Reference
  Authors
Namavar Y, Chitayat D, Barth PG, van Ruissen F, de Wissel MB, Poll-The BT, Silver R, Baas F
  Title
TSEN54 mutations cause pontocerebellar hypoplasia type 5.
  Journal
Eur J Hum Genet 19:724-6 (2011)
DOI:10.1038/ejhg.2011.8
Reference
  Authors
Agamy O, Ben Zeev B, Lev D, Marcus B, Fine D, Su D, Narkis G, Ofir R, Hoffmann C, Leshinsky-Silver E, Flusser H, Sivan S, Soll D, Lerman-Sagie T, Birk OS
  Title
Mutations disrupting selenocysteine formation cause progressive cerebello-cerebral atrophy.
  Journal
Am J Hum Genet 87:538-44 (2010)
DOI:10.1016/j.ajhg.2010.09.007
Reference
  Authors
Feinstein M, Flusser H, Lerman-Sagie T, Ben-Zeev B, Lev D, Agamy O, Cohen I, Kadir R, Sivan S, Leshinsky-Silver E, Markus B, Birk OS
  Title
VPS53 mutations cause progressive cerebello-cerebral atrophy type 2 (PCCA2).
  Journal
J Med Genet 51:303-8 (2014)
DOI:10.1136/jmedgenet-2013-101823
Reference
  Authors
Breuss MW, Sultan T, James KN, Rosti RO, Scott E, Musaev D, Furia B, Reis A, Sticht H, Al-Owain M, Alkuraya FS, Reuter MS, Abou Jamra R, Trotta CR, Gleeson JG
  Title
Autosomal-Recessive Mutations in the tRNA Splicing Endonuclease Subunit TSEN15 Cause Pontocerebellar Hypoplasia and Progressive Microcephaly.
  Journal
Am J Hum Genet 99:228-35 (2016)
DOI:10.1016/j.ajhg.2016.05.023
Reference
  Authors
Ahmed MY, Chioza BA, Rajab A, Schmitz-Abe K, Al-Khayat A, Al-Turki S, Baple EL, Patton MA, Al-Memar AY, Hurles ME, Partlow JN, Hill RS, Evrony GD, Servattalab S, Markianos K, Walsh CA, Crosby AH, Mochida GH
  Title
Loss of PCLO function underlies pontocerebellar hypoplasia type III.
  Journal
Neurology 84:1745-50 (2015)
DOI:10.1212/WNL.0000000000001523
Reference
  Authors
Lardelli RM, Schaffer AE, Eggens VR, Zaki MS, Grainger S, Sathe S, Van Nostrand EL, Schlachetzki Z, Rosti B, Akizu N, Scott E, Silhavy JL, Heckman LD, Rosti RO, Dikoglu E, Gregor A, Guemez-Gamboa A, Musaev D, Mande R, Widjaja A, Shaw TL, Markmiller S, Marin-Valencia I, Davies JH, de Meirleir L, Kayserili H, Altunoglu U, Freckmann ML, Warwick L, Chitayat D, Blaser S, Caglayan AO, Bilguvar K, Per H, Fagerberg C, Christesen HT, Kibaek M, Aldinger KA, Manchester D, Matsumoto N, Muramatsu K, Saitsu H, Shiina M, Ogata K, Foulds N, Dobyns WB, Chi NC, Traver D, Spaccini L, Bova SM, Gabriel SB, Gunel M, Valente EM, Nassogne MC, Bennett EJ, Yeo GW, Baas F, Lykke-Andersen J, Gleeson JG
  Title
Biallelic mutations in the 3' exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing.
  Journal
Nat Genet 49:457-464 (2017)
DOI:10.1038/ng.3762
Reference
  Authors
Mochida GH, Ganesh VS, de Michelena MI, Dias H, Atabay KD, Kathrein KL, Huang HT, Hill RS, Felie JM, Rakiec D, Gleason D, Hill AD, Malik AN, Barry BJ, Partlow JN, Tan WH, Glader LJ, Barkovich AJ, Dobyns WB, Zon LI, Walsh CA
  Title
CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development.
  Journal
Nat Genet 44:1260-4 (2012)
DOI:10.1038/ng.2425
Reference
  Authors
Akizu N, Cantagrel V, Schroth J, Cai N, Vaux K, McCloskey D, Naviaux RK, Van Vleet J, Fenstermaker AG, Silhavy JL, Scheliga JS, Toyama K, Morisaki H, Sonmez FM, Celep F, Oraby A, Zaki MS, Al-Baradie R, Faqeih EA, Saleh MA, Spencer E, Rosti RO, Scott E, Nickerson E, Gabriel S, Morisaki T, Holmes EW, Gleeson JG
  Title
AMPD2 regulates GTP synthesis and is mutated in a potentially treatable neurodegenerative brainstem disorder.
  Journal
Cell 154:505-17 (2013)
DOI:10.1016/j.cell.2013.07.005
Reference
  Authors
Karaca E, Weitzer S, Pehlivan D, Shiraishi H, Gogakos T, Hanada T, Jhangiani SN, Wiszniewski W, Withers M, Campbell IM, Erdin S, Isikay S, Franco LM, Gonzaga-Jauregui C, Gambin T, Gelowani V, Hunter JV, Yesil G, Koparir E, Yilmaz S, Brown M, Briskin D, Hafner M, Morozov P, Farazi TA, Bernreuther C, Glatzel M, Trattnig S, Friske J, Kronnerwetter C, Bainbridge MN, Gezdirici A, Seven M, Muzny DM, Boerwinkle E, Ozen M, Clausen T, Tuschl T, Yuksel A, Hess A, Gibbs RA, Martinez J, Penninger JM, Lupski JR
  Title
Human CLP1 mutations alter tRNA biogenesis, affecting both peripheral and central nervous system function.
  Journal
Cell 157:636-50 (2014)
DOI:10.1016/j.cell.2014.02.058

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