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
Brite
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
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06541 Cytoskeleton in neurons
H00897 Pontocerebellar hypoplasia
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
