H00897 [KEGG MEDICUS

Kegg medicus disease en

H00897
H number	H00897
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	Congenital malformation
Network	-
Gene	(PCH1A) VRK1 [HSA:7443] [KO:K08816] (PCH1B) EXOSC3 [HSA:51010] [KO:K03681] (PCH1C) EXOSC8 [HSA:11340] [KO:K12586] (PCH1D) EXOSC9 [HSA:5393] [KO:K03678] (PCH1E) SLC25A46 [HSA:91137] [KO:K03454] (PCH1F) EXOSC1 [HSA:51013] [KO:K07573] (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] (PCH11) TBC1D23 [HSA:55773] [KO:K22555] (PCH12) COASY [HSA:80347] [KO:K02318] (PCH13) VPS51 [HSA:738] [KO:K20296] (PCH14) PPIL1 [HSA:51645] [KO:K12733] (PCH15) CDC40 [HSA:51362] [KO:K12816] (PCH16) MINPP1 [HSA:9562] [KO:K03103] (PCH17) PRDM13 [HSA:59336] [KO:K24645]
Pathogen	-
Env factor	-
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Comment	-
Other DBs	ICD-11: LD20.01 ICD-10: Q04.3 MeSH: C580383 OMIM: 607596 614678 616081 618065 619303 619304 277470 225753 612389 612390 611523 608027 613811 615851 617026 614969 614961 615809 615803 617695 618266 618606 619301 619302 619527 619909
Reference	PMID:21749694 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 PMID:19646678 (PCH1A) AUTHORS Renbaum P, Kellerman E, Jaron R, Geiger D, Segel R, Lee M, King MC, Levy-Lahad E TITLE Spinal muscular atrophy with pontocerebellar hypoplasia is caused by a mutation in the VRK1 gene. JOURNAL Am J Hum Genet 85:281-9 (2009) DOI:10.1016/j.ajhg.2009.07.006 PMID:23564332 (PCH1B) 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 PMID:24989451 (PCH1C) 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 PMID:29727687 (PCH1D) AUTHORS Burns DT, Donkervoort S, Muller JS, Knierim E, Bharucha-Goebel D, Faqeih EA, Bell SK, AlFaifi AY, Monies D, Millan F, Retterer K, Dyack S, MacKay S, Morales-Gonzalez S, Giunta M, Munro B, Hudson G, Scavina M, Baker L, Massini TC, Lek M, Hu Y, Ezzo D, AlKuraya FS, Kang PB, Griffin H, Foley AR, Schuelke M, Horvath R, Bonnemann CG TITLE Variants in EXOSC9 Disrupt the RNA Exosome and Result in Cerebellar Atrophy with Spinal Motor Neuronopathy. JOURNAL Am J Hum Genet 102:858-873 (2018) DOI:10.1016/j.ajhg.2018.03.011 PMID:26168012 (PCH1E) AUTHORS Abrams AJ, Hufnagel RB, Rebelo A, Zanna C, Patel N, Gonzalez MA, Campeanu IJ, Griffin LB, Groenewald S, Strickland AV, Tao F, Speziani F, Abreu L, Schule R, Caporali L, La Morgia C, Maresca A, Liguori R, Lodi R, Ahmed ZM, Sund KL, Wang X, Krueger LA, Peng Y, Prada CE, Prows CA, Schorry EK, Antonellis A, Zimmerman HH, Abdul-Rahman OA, Yang Y, Downes SM, Prince J, Fontanesi F, Barrientos A, Nemeth AH, Carelli V, Huang T, Zuchner S, Dallman JE TITLE Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder. JOURNAL Nat Genet 47:926-32 (2015) DOI:10.1038/ng.3354 PMID:33463720 (PCH1F) AUTHORS Somashekar PH, Kaur P, Stephen J, Guleria VS, Kadavigere R, Girisha KM, Bielas S, Upadhyai P, Shukla A TITLE Bi-allelic missense variant, p.Ser35Leu in EXOSC1 is associated with pontocerebellar hypoplasia. JOURNAL Clin Genet 99:594-600 (2021) DOI:10.1111/cge.13928 PMID:21368912 (PCH2A/4/5) 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 PMID:18711368 (PCH2B PCH2C) AUTHORS Budde BS, Namavar Y, Barth PG, Poll-The BT, Nurnberg G, Becker C, van Ruissen F, Weterman MA, Fluiter K, te Beek ET, Aronica E, van der Knaap MS, Hohne W, Toliat MR, Crow YJ, Steinling M, Voit T, Roelenso F, Brussel W, Brockmann K, Kyllerman M, Boltshauser E, Hammersen G, Willemsen M, Basel-Vanagaite L, Krageloh-Mann I, de Vries LS, Sztriha L, Muntoni F, Ferrie CD, Battini R, Hennekam RC, Grillo E, Beemer FA, Stoets LM, Wollnik B, Nurnberg P, Baas F TITLE tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia. JOURNAL Nat Genet 40:1113-8 (2008) DOI:10.1038/ng.204 PMID:20920667 (PCH2D) 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 PMID:24577744 (PCH2E) 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 PMID:27392077 (PCH2F) 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 PMID:25832664 (PCH3) 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 PMID:17847012 (PCH6) AUTHORS Edvardson S, Shaag A, Kolesnikova O, Gomori JM, Tarassov I, Einbinder T, Saada A, Elpeleg O TITLE Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia. JOURNAL Am J Hum Genet 81:857-62 (2007) DOI:10.1086/521227 PMID:28092684 (PCH7) 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 PMID:23023333 (PCH8) 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 PMID:23911318 (PCH9) 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 PMID:24766809 (PCH10) 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 PMID:28823707 (PCH11) AUTHORS Ivanova EL, Mau-Them FT, Riazuddin S, Kahrizi K, Laugel V, Schaefer E, de Saint Martin A, Runge K, Iqbal Z, Spitz MA, Laura M, Drouot N, Gerard B, Deleuze JF, de Brouwer APM, Razzaq A, Dollfus H, Assir MZ, Nitchke P, Hinckelmann MV, Ropers H, Riazuddin S, Najmabadi H, van Bokhoven H, Chelly J TITLE Homozygous Truncating Variants in TBC1D23 Cause Pontocerebellar Hypoplasia and Alter Cortical Development. JOURNAL Am J Hum Genet 101:428-440 (2017) DOI:10.1016/j.ajhg.2017.07.010 PMID:30089828 (PCH12) AUTHORS van Dijk T, Ferdinandusse S, Ruiter JPN, Alders M, Mathijssen IB, Parboosingh JS, Innes AM, Meijers-Heijboer H, Poll-The BT, Bernier FP, Wanders RJA, Lamont RE, Baas F TITLE Biallelic loss of function variants in COASY cause prenatal onset pontocerebellar hypoplasia, microcephaly, and arthrogryposis. JOURNAL Eur J Hum Genet 26:1752-1758 (2018) DOI:10.1038/s41431-018-0233-0 PMID:31207318 (PCH13) AUTHORS Uwineza A, Caberg JH, Hitayezu J, Wenric S, Mutesa L, Vial Y, Drunat S, Passemard S, Verloes A, El Ghouzzi V, Bours V TITLE VPS51 biallelic variants cause microcephaly with brain malformations: A confirmatory report. JOURNAL Eur J Med Genet 62:103704 (2019) DOI:10.1016/j.ejmg.2019.103704 PMID:33220177 (PCH14 PCH15) AUTHORS Chai G, Webb A, Li C, Antaki D, Lee S, Breuss MW, Lang N, Stanley V, Anzenberg P, Yang X, Marshall T, Gaffney P, Wierenga KJ, Chung BH, Tsang MH, Pais LS, Lovgren AK, VanNoy GE, Rehm HL, Mirzaa G, Leon E, Diaz J, Neumann A, Kalverda AP, Manfield IW, Parry DA, Logan CV, Johnson CA, Bonthron DT, Valleley EMA, Issa MY, Abdel-Ghafar SF, Abdel-Hamid MS, Jennings P, Zaki MS, Sheridan E, Gleeson JG TITLE Mutations in Spliceosomal Genes PPIL1 and PRP17 Cause Neurodegenerative Pontocerebellar Hypoplasia with Microcephaly. JOURNAL Neuron 109:241-256.e9 (2021) DOI:10.1016/j.neuron.2020.10.035 PMID:33168985 (PCH16) AUTHORS Appelhof B, Wagner M, Hoefele J, Heinze A, Roser T, Koch-Hogrebe M, Roosendaal SD, Dehghani M, Mehrjardi MYV, Torti E, Houlden H, Maroofian R, Rajabi F, Sticht H, Baas F, Wieczorek D, Jamra RA TITLE Pontocerebellar hypoplasia due to bi-allelic variants in MINPP1. JOURNAL Eur J Hum Genet 29:411-421 (2021) DOI:10.1038/s41431-020-00749-x PMID:35390279 (PCH17) AUTHORS Coolen M, Altin N, Rajamani K, Pereira E, Siquier-Pernet K, Puig Lombardi E, Moreno N, Barcia G, Yvert M, Laquerriere A, Pouliet A, Nitschke P, Boddaert N, Rausell A, Razavi F, Afenjar A, Billette de Villemeur T, Al-Maawali A, Al-Thihli K, Baptista J, Beleza-Meireles A, Garel C, Legendre M, Gelot A, Burglen L, Moutton S, Cantagrel V TITLE Recessive PRDM13 mutations cause fatal perinatal brainstem dysfunction with cerebellar hypoplasia and disrupt Purkinje cell differentiation. JOURNAL Am J Hum Genet 109:909-927 (2022) DOI:10.1016/j.ajhg.2022.03.010

KEGG MEDICUS - Disease