Pontocerebellar hypoplasia due to bi-allelic variants in MINPP1.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
25
06
2020
accepted:
22
09
2020
revised:
11
09
2020
pubmed:
11
11
2020
medline:
15
1
2022
entrez:
10
11
2020
Statut:
ppublish
Résumé
Pontocerebellar hypoplasia (PCH) describes a group of rare heterogeneous neurodegenerative diseases with prenatal onset. Here we describe eight children with PCH from four unrelated families harboring the homozygous MINPP1 (NM_004897.4) variants; c.75_94del, p.(Leu27Argfs*39), c.851 C > A, p.(Ala284Asp), c.1210 C > T, p.(Arg404*), and c.992 T > G, p.(Ile331Ser). The homozygous p.(Leu27Argfs*39) change is predicted to result in a complete absence of MINPP1. The p.(Arg404*) would likely lead to a nonsense mediated decay, or alternatively, a loss of several secondary structure elements impairing protein folding. The missense p.(Ala284Asp) affects a buried, hydrophobic residue within the globular domain. The introduction of aspartic acid is energetically highly unfavorable and therefore predicted to cause a significant reduction in protein stability. The missense p.(Ile331Ser) affects the tight hydrophobic interactions of the isoleucine by the disruption of the polar side chain of serine, destabilizing the structure of MINPP1. The overlap of the above-mentioned genotypes and phenotypes is highly improbable by chance. MINPP1 is the only enzyme that hydrolyses inositol phosphates in the endoplasmic reticulum lumen and several studies support its role in stress induced apoptosis. The pathomechanism explaining the disease mechanism remains unknown, however several others genes of the inositol phosphatase metabolism (e.g., INPP5K, FIG4, INPP5E, ITPR1) are correlated with phenotypes of neurodevelopmental disorders. Taken together, we present MINPP1 as a novel autosomal recessive pontocerebellar hypoplasia gene.
Identifiants
pubmed: 33168985
doi: 10.1038/s41431-020-00749-x
pii: 10.1038/s41431-020-00749-x
pmc: PMC7940488
doi:
Substances chimiques
Codon, Nonsense
0
Phosphoric Monoester Hydrolases
EC 3.1.3.2
multiple inositol-polyphosphate phosphatase
EC 3.1.3.62
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
411-421Subventions
Organisme : Department of Health
Pays : United Kingdom
Références
Budde BS, Namavar Y, Barth PG, Poll-The BT, Nurnberg G, Becker C, et al. tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia. Nat Genet. 2008;40:1113–8.
pubmed: 18711368
Appelhof B, Barth PG, Baas F. Classification of pontocerebellar hypoplasia: where does it end? Eur Med J Neurol. 2019;7:52–61.
Namavar Y, Barth PG, Kasher PR, van Ruissen F, Brockmann K, Bernert G, et al. Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. Brain 2011;134:143–56.
pubmed: 20952379
Schaffer Ashleigh E, Eggens Veerle RC, Caglayan Ahmet O, Reuter Miriam S, Scott E, Coufal Nicole G, et al. CLP1 founder mutation links tRNA splicing and maturation to cerebellar development and neurodegeneration. Cell 2014;157:651–63.
pubmed: 24766810
pmcid: 4128918
Ahmed MY, Chioza BA, Rajab A, Schmitz-Abe K, Al-Khayat A, Al-Turki S, et al. Loss of PCLO function underlies pontocerebellar hypoplasia type III. Neurology 2015;84:1745–50.
pubmed: 25832664
pmcid: 4424132
Breuss MW, Sultan T, James KN, Rosti RO, Scott E, Musaev D, et al. Autosomal-recessive mutations in the tRNA splicing endonuclease subunit TSEN15 cause pontocerebellar hypoplasia and progressive microcephaly. Am J Hum Genet. 2016;99:228–35.
pubmed: 27392077
pmcid: 5005448
Mochida GH, Ganesh VS, de Michelena MI, Dias H, Atabay KD, Kathrein KL, et al. CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development. Nat Genet. 2012;44:1260–4.
pubmed: 23023333
pmcid: 3567443
Marin-Valencia I, Gerondopoulos A, Zaki MS, Ben-Omran T, Almureikhi M, Demir E, et al. Homozygous mutations in TBC1D23 lead to a non-degenerative form of pontocerebellar hypoplasia. Am J Hum Genet. 2017;101:441–50.
pubmed: 28823706
pmcid: 5590949
Lardelli RM, Schaffer AE, Eggens VR, Zaki MS, Grainger S, Sathe S, et al. Biallelic mutations in the 3’ exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing. Nat Genet. 2017;49:457–64.
pubmed: 28092684
pmcid: 5325768
Renbaum P, Kellerman E, Jaron R, Geiger D, Segel R, Lee M, et al. Spinal muscular atrophy with pontocerebellar hypoplasia is caused by a mutation in the VRK1 gene. Am J Hum Genet. 2009;85:281–9.
pubmed: 19646678
pmcid: 2725266
Burns DT, Donkervoort S, Muller JS, Knierim E, Bharucha-Goebel D, Faqeih EA, et al. Variants in EXOSC9 disrupt the RNA exosome and result in cerebellar atrophy with spinal motor neuronopathy. Am J Hum Genet. 2018;102:858–73.
pubmed: 29727687
pmcid: 5986733
Rudnik-Schoneborn S, Senderek J, Jen JC, Houge G, Seeman P, Puchmajerova A, et al. Pontocerebellar hypoplasia type 1: clinical spectrum and relevance of EXOSC3 mutations. Neurology 2013;80:438–46.
pubmed: 23284067
pmcid: 3590055
Boczonadi V, Muller JS, Pyle A, Munkley J, Dor T, Quartararo J, et al. EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia. Nat Commun. 2014;5:4287.
pubmed: 24989451
Feinstein M, Flusser H, Lerman-Sagie T, Ben-Zeev B, Lev D, Agamy O, et al. VPS53 mutations cause progressive cerebello-cerebral atrophy type 2 (PCCA2). J Med Genet. 2014;51:303–8.
pubmed: 24577744
van Dijk T, Ferdinandusse S, Ruiter JPN, Alders M, Mathijssen IB, Parboosingh JS, et al. Biallelic loss of function variants in COASY cause prenatal onset pontocerebellar hypoplasia, microcephaly, and arthrogryposis. Eur J Hum Genet. 2018;26:1752–8.
pubmed: 30089828
pmcid: 6244412
van Dijk T, Rudnik-Schoneborn S, Senderek J, Hajmousa G, Mei H, Dusl M, et al. Pontocerebellar hypoplasia with spinal muscular atrophy (PCH1): identification of SLC25A46 mutations in the original Dutch PCH1 family. Brain 2017;140:e46.
pubmed: 28637197
Ali N, Craxton A, Shears SB. Hepatic Ins(1,3,4,5)P4 3-phosphatase is compartmentalized inside endoplasmic reticulum. J Biol Chem. 1993;268:6161–7.
pubmed: 8384201
Sobreira N, Schiettecatte F, Valle D, Hamosh A. GeneMatcher: a matching tool for connecting investigators with an interest in the same gene. Hum Mutat. 2015;36:928–30.
pubmed: 26220891
pmcid: 4833888
Makrythanasis P, Maroofian R, Stray-Pedersen A, Musaev D, Zaki MS, Mahmoud IG, et al. Biallelic variants in KIF14 cause intellectual disability with microcephaly. Eur J Hum Genet. 2018;26:330–9.
pubmed: 29343805
pmcid: 5839044
Brunet T, Radivojkov-Blagojevic M, Lichtner P, Kraus V, Meitinger T, Wagner M. Biallelic loss-of-function variants in RBL2 in siblings with a neurodevelopmental disorder. Ann Clin Transl Neurol. 2020;7:390–6.
pubmed: 32105419
pmcid: 7086002
Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, et al. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 2014;42:D980–5.
pubmed: 24234437
Stenson PD, Ball EV, Mort M, Phillips AD, Shiel JA, Thomas NS, et al. Human gene mutation database (HGMD): 2003 update. Hum Mutat. 2003;21:577–81.
pubmed: 12754702
Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 2016;536:285–91.
pubmed: 27535533
pmcid: 5018207
Oakley AJ. The structure of Aspergillus niger phytase PhyA in complex with a phytate mimetic. Biochem Biophys Res Commun. 2010;397:745–9.
pubmed: 20541524
Zimmermann L, Stephens A, Nam SZ, Rau D, Kubler J, Lozajic M, et al. A completely reimplemented MPI bioinformatics toolkit with a New HHpred server at its core. J Mol Biol. 2018;430:2237–43.
pubmed: 29258817
Webb B, Sali A. Protein structure modeling with MODELLER. Methods Mol Biol. 2017;1654:39–54.
pubmed: 28986782
Baugh EH, Simmons-Edler R, Muller CL, Alford RF, Volfovsky N, Lash AE, et al. Robust classification of protein variation using structural modelling and large-scale data integration. Nucleic Acids Res. 2016;44:2501–13.
pubmed: 26926108
pmcid: 4824117
Sayle R. RASMOL: biomolecular graphics for all. Trends Biochemical Sci. 1995;20:374–6.
Ucuncu E, Rajamani K, Wilson MSC, Medina-Cano D, Altin N, David P, et al. MINPP1 prevents intracellular accumulation of the cation chelator inositol hexakisphosphate and is mutated in Pontocerebellar Hypoplasia. 2020.
Berridge MJ, Irvine RF. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 1984;312:315–21.
pubmed: 6095092
Berridge MJ, Irvine RF. Inositol phosphates and cell signalling. Nature 1989;341:197–205.
pubmed: 2550825
Chakraborty A, Koldobskiy MA, Bello NT, Maxwell M, Potter JJ, Juluri KR, et al. Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain. Cell 2010;143:897–910.
pubmed: 21145457
pmcid: 3052691
Irvine RF, Schell MJ. Back in the water: the return of the inositol phosphates. Nat Rev Mol Cell Biol. 2001;2:327–38.
pubmed: 11331907
York JD, Odom AR, Murphy R, Ives EB, Wente SR. A phospholipase C-dependent inositol polyphosphate kinase pathway required for efficient messenger RNA export. Science 1999;285:96–100.
pubmed: 10390371
Ali N, Craxton A, Sumner M, Shears SB. Effects of aluminium on the hepatic inositol polyphosphate phosphatase. Biochem J. 1995;305:557–61.
pubmed: 7832774
pmcid: 1136398
Caffrey JJ, Hidaka K, Matsuda M, Hirata M, Shears SB. The human and rat forms of multiple inositol polyphosphate phosphatase: functional homology with a histidine acid phosphatase up-regulated during endochondral ossification. FEBS Lett. 1999;442:99–104.
pubmed: 9923613
Chi H, Tiller GE, Dasouki MJ, Romano PR, Wang J, O’Keefe RJ, et al. Multiple inositol polyphosphate phosphatase: evolution as a distinct group within the histidine phosphatase family and chromosomal localization of the human and mouse genes to chromosomes 10q23 and 19. Genomics. 1999;56:324–36.
pubmed: 10087200
Agarwal R, Mumtaz H, Ali N. Role of inositol polyphosphates in programmed cell death. Mol Cell Biochem. 2009;328:155–65.
pubmed: 19322641
Agarwal R, Hassen S, Ali N. Changes in cellular levels of inositol polyphosphates during apoptosis. Mol Cell Biochem. 2010;345:61–8.
pubmed: 20725767
Cho J, King JS, Qian X, Harwood AJ, Shears SB. Dephosphorylation of 2,3-bisphosphoglycerate by MIPP expands the regulatory capacity of the Rapoport-Luebering glycolytic shunt. Proc Natl Acad Sci USA. 2008;105:5998–6003.
pubmed: 18413611
pmcid: 2329705
Helmis C, Blechner C, Lin H, Schweizer M, Mayr GW, Nielsen P, et al. Malignant H1299 tumour cells preferentially internalize iron-bound inositol hexakisphosphate. Biosci Rep. 2013;33:815–22.
Kilaparty SP, Agarwal R, Singh P, Kannan K, Ali N. Endoplasmic reticulum stress-induced apoptosis accompanies enhanced expression of multiple inositol polyphosphate phosphatase 1 (Minpp1): a possible role for Minpp1 in cellular stress response. Cell Stress Chaperones. 2016;21:593–608.
pubmed: 27038811
pmcid: 4907990
Chi H, Yang X, Kingsley PD, O’Keefe RJ, Puzas JE, Rosier RN, et al. Targeted deletion of Minpp1 provides new insight into the activity of multiple inositol polyphosphate phosphatase in vivo. Mol Cell Biol. 2000;20:6496–507.
pubmed: 10938126
pmcid: 86124
van Dijk T, Barth P, Reneman L, Appelhof B, Baas F, Poll-The BT. A de novo missense mutation in the inositol 1,4,5-triphosphate receptor type 1 gene causing severe pontine and cerebellar hypoplasia: expanding the phenotype of ITPR1-related spinocerebellar ataxia’s. Am J Med Genet A 2017;173:207–12.
pubmed: 27862915
Wiessner M, Roos A, Munn CJ, Viswanathan R, Whyte T, Cox D, et al. Mutations in INPP5K, encoding a phosphoinositide 5-phosphatase, cause congenital muscular dystrophy with cataracts and mild cognitive impairment. Am J Hum Genet. 2017;100:523–36.
pubmed: 28190456
pmcid: 5339217
Reutter H, Bagci S, Muller A, Gembruch U, Geipel A, Berg C, et al. Primary pulmonary hypertension, congenital heart defect, central nervous system malformations, hypo- and aplastic toes: another case of Yunis-Varon syndrome or report of a new entity. Eur J Med Genet. 2012;55:27–31.
pubmed: 22044576
Hampshire DJ, Ayub M, Springell K, Roberts E, Jafri H, Rashid Y, et al. MORM syndrome (mental retardation, truncal obesity, retinal dystrophy and micropenis), a new autosomal recessive disorder, links to 9q34. Eur J Hum Genet. 2006;14:543–8.
pubmed: 16493448