J. A. Sullivan, K. Shirasu, and X. W. Deng, The diverse roles of ubiquitin and the 26S proteasome in the life of plants, Nature Reviews Genetics, vol.34, issue.12, pp.948-958, 2003.
DOI : 10.1046/j.1365-313X.2003.01768.x

A. L. Goldberg, Protein degradation and protection against misfolded or damaged proteins, Nature, vol.61, issue.6968, pp.895-899, 2003.
DOI : 10.1128/MCB.19.4.2547

A. Hershko and A. Ciechanover, THE UBIQUITIN SYSTEM, Annual Review of Biochemistry, vol.67, issue.1, pp.425-479, 1998.
DOI : 10.1146/annurev.biochem.67.1.425

D. Finley, Recognition and Processing of Ubiquitin-Protein Conjugates by the Proteasome, Annual Review of Biochemistry, vol.78, issue.1, pp.477-513, 2009.
DOI : 10.1146/annurev.biochem.78.081507.101607

S. Murata, H. Yashiroda, and K. Tanaka, Molecular mechanisms of proteasome assembly, Nature Reviews Molecular Cell Biology, vol.38, issue.2, pp.104-115, 2009.
DOI : 10.4049/jimmunol.176.11.6665

D. Voges, P. Zwickl, and W. Baumeister, The 26S Proteasome: A Molecular Machine Designed for Controlled Proteolysis, Annual Review of Biochemistry, vol.68, issue.1, pp.1015-1068, 1999.
DOI : 10.1146/annurev.biochem.68.1.1015

A. M. Hamilton and K. Zito, Breaking It Down: The Ubiquitin Proteasome System in Neuronal Morphogenesis, Neural Plasticity, vol.4, issue.10, article e7598, 2013.
DOI : 10.1038/emboj.2011.482
URL : http://downloads.hindawi.com/journals/np/2013/196848.pdf

H. C. Tai and E. M. Schuman, Ubiquitin, the proteasome and protein degradation in neuronal function and dysfunction, Nature Reviews Neuroscience, vol.3, issue.11, pp.826-838, 2008.
DOI : 10.4161/auto.4144

I. J. Cajigas, T. Will, and E. M. Schuman, Protein homeostasis and synaptic plasticity, The EMBO Journal, vol.23, issue.16, pp.2746-2752, 2010.
DOI : 10.1086/512489
URL : http://emboj.embopress.org/content/embojnl/29/16/2746.full.pdf

A. N. Hegde, K. A. Haynes, S. V. Bach, and B. C. Beckelman, Local ubiquitin-proteasome-mediated proteolysis and long-term synaptic plasticity, Frontiers in Molecular Neuroscience, vol.13, p.96, 2014.
DOI : 10.1016/S0960-9822(03)00332-4
URL : http://journal.frontiersin.org/article/10.3389/fnmol.2014.00096/pdf

F. Acconcia, S. Sigismund, and S. Polo, Ubiquitin in trafficking: The network at work, Experimental Cell Research, vol.315, issue.9, pp.1610-1618, 2009.
DOI : 10.1016/j.yexcr.2008.10.014

L. A. Schwarz, P. , and G. N. , Ubiquitin-dependent endocytosis, trafficking and turnover of neuronal membrane proteins, Molecular and Cellular Neuroscience, vol.49, issue.3, pp.387-393, 2012.
DOI : 10.1016/j.mcn.2011.08.006
URL : http://europepmc.org/articles/pmc3279607?pdf=render

N. P. Dantuma and L. C. Bott, The ubiquitin-proteasome system in neurodegenerative diseases: precipitating factor, yet part of the solution, Frontiers in Molecular Neuroscience, vol.30, p.70, 2014.
DOI : 10.1038/emboj.2011.224

F. Fecto, Y. T. Esengul, and T. Siddique, Protein recycling pathways in neurodegenerative diseases, Alzheimer's Research & Therapy, vol.6, issue.2, p.13, 2014.
DOI : 10.1016/j.exger.2010.08.030
URL : https://alzres.biomedcentral.com/track/pdf/10.1186/alzrt243?site=alzres.biomedcentral.com

T. Kishino, M. Lalande, and J. Wagstaff, UBE3A/E6-AP mutations cause Angelman syndrome, Nature Genetics, vol.6, issue.1, pp.70-73, 1997.
DOI : 10.1038/ng0194-98

L. Basel-vanagaite, B. Dallapiccola, R. Ramirez-solis, A. Segref, H. Thiele et al., Deficiency for the Ubiquitin Ligase UBE3B in a Blepharophimosis-Ptosis-Intellectual-Disability Syndrome, The American Journal of Human Genetics, vol.91, issue.6, pp.998-1010, 2012.
DOI : 10.1016/j.ajhg.2012.10.011
URL : https://hal.archives-ouvertes.fr/pasteur-01375146

G. Froyen, M. Corbett, J. Vandewalle, I. Jarvela, O. Lawrence et al., Submicroscopic Duplications of the Hydroxysteroid Dehydrogenase HSD17B10 and the E3 Ubiquitin Ligase HUWE1 Are Associated with Mental Retardation, The American Journal of Human Genetics, vol.82, issue.2, pp.432-443, 2008.
DOI : 10.1016/j.ajhg.2007.11.002

Y. H. Hao, M. D. Fountain, . Jr, K. Fon-tacer, F. Xia et al., USP7 Acts as a Molecular Rheostat to Promote WASH-Dependent Endosomal Protein Recycling and Is Mutated in a Human Neurodevelopmental Disorder, Molecular Cell, vol.59, issue.6, pp.956-969, 2015.
DOI : 10.1016/j.molcel.2015.07.033
URL : https://doi.org/10.1016/j.molcel.2015.07.033

C. C. Homan, R. Kumar, L. S. Nguyen, E. Haan, F. L. Raymond et al., Mutations in USP9X Are Associated with X-Linked Intellectual Disability and Disrupt Neuronal Cell Migration and Growth, The American Journal of Human Genetics, vol.94, issue.3, pp.470-478, 2014.
DOI : 10.1016/j.ajhg.2014.02.004
URL : https://doi.org/10.1016/j.ajhg.2014.02.004

N. Sobreira, F. Schiettecatte, D. Valle, and A. Hamosh, GeneMatcher: A Matching Tool for Connecting Investigators with an Interest in the Same Gene, Human Mutation, vol.312, issue.Database issue, pp.928-930, 2015.
DOI : 10.1001/jama.2014.14601

H. V. Firth, S. M. Richards, A. P. Bevan, S. Clayton, M. Corpas et al., DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources, The American Journal of Human Genetics, vol.84, issue.4, pp.524-533, 2009.
DOI : 10.1016/j.ajhg.2009.03.010

B. Isidor, S. Küry, J. A. Rosenfeld, T. Besnard, S. Schmitt et al., Cause Syndromic Intellectual Disability, Human Mutation, vol.142, issue.Database issue, pp.354-358, 2016.
DOI : 10.1016/j.cell.2010.08.020
URL : https://hal.archives-ouvertes.fr/hal-01259225

K. Retterer, J. Juusola, M. T. Cho, P. Vitazka, F. Millan et al., Clinical application of whole-exome sequencing across clinical indications, Genetics in Medicine, vol.11, issue.7, pp.696-704, 2016.
DOI : 10.1007/s10048-015-0454-0

I. Iossifov, B. J. O-'roak, S. J. Sanders, M. Ronemus, N. Krumm et al., The contribution of de novo coding mutations to autism spectrum disorder, Nature, vol.43, issue.7526, pp.216-221, 2014.
DOI : 10.1038/ng.902
URL : http://europepmc.org/articles/pmc4313871?pdf=render

, The American Journal of Human Genetics, vol.100, pp.352-363, 2017.

M. N. Bainbridge, M. Wang, Y. Wu, I. Newsham, D. M. Muzny et al., Targeted enrichment beyond the consensus coding DNA sequence exome reveals exons with higher variant densities, Genome Biology, vol.12, issue.7, p.68, 2011.
DOI : 10.1093/bioinformatics/btp324

Y. Yang, D. M. Muzny, J. G. Reid, M. N. Bainbridge, A. Willis et al., Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders, New England Journal of Medicine, vol.369, issue.16, pp.1502-1511, 2013.
DOI : 10.1056/NEJMoa1306555

P. M. Boone, C. A. Bacino, C. A. Shaw, P. A. Eng, P. M. Hixson et al., Detection of clinically relevant exonic copy-number changes by array CGH, Human Mutation, vol.91, issue.12, pp.1326-1342, 2010.
DOI : 10.1007/BF00218258

J. Wiszniewska, W. Bi, C. Shaw, P. Stankiewicz, S. H. Kang et al., Combined array CGH plus SNP genome analyses in a single assay for optimized clinical testing, European Journal of Human Genetics, vol.36, issue.1, pp.79-87, 2014.
DOI : 10.1002/cncr.27556

J. R. Macdonald, R. Ziman, R. K. Yuen, L. Feuk, and S. W. Scherer, The Database of Genomic Variants: a curated collection of structural variation in the human genome, Nucleic Acids Research, vol.7, issue.D1, pp.986-992, 2014.
DOI : 10.1002/humu.22049

A. V. Gomes, Genetics of proteasome diseases. Scientifica (Cairo) 2013, p.637629, 2013.

S. Bhattacharyya, H. Yu, C. Mim, and A. Matouschek, Regulated protein turnover: snapshots of the proteasome in action, Nature Reviews Molecular Cell Biology, vol.170, issue.2, pp.122-133, 2014.
DOI : 10.1016/j.jsb.2010.03.007

M. Sharon, T. Taverner, X. I. Ambroggio, R. J. Deshaies, R. et al., Structural Organization of the 19S Proteasome Lid: Insights from MS of Intact Complexes, PLoS Biology, vol.279, issue.8, p.267, 2006.
DOI : 10.1371/journal.pbio.0040267.t004

M. H. Glickman, D. M. Rubin, O. Coux, I. Wefes, G. Pfeifer et al., A Subcomplex of the Proteasome Regulatory Particle Required for Ubiquitin-Conjugate Degradation and Related to the COP9-Signalosome and eIF3, Cell, vol.94, issue.5, pp.615-623, 1998.
DOI : 10.1016/S0092-8674(00)81603-7

D. M. Rubin, M. H. Glickman, C. N. Larsen, S. Dhruvakumar, F. et al., Active site mutants in the six regulatory particle ATPases reveal multiple roles for ATP in the proteasome, The EMBO Journal, vol.17, issue.17, pp.4909-4919, 1998.
DOI : 10.1093/emboj/17.17.4909

A. J. Book, J. Smalle, K. H. Lee, P. Yang, J. M. Walker et al., The RPN5 Subunit of the 26s Proteasome Is Essential for Gametogenesis, Sporophyte Development, and Complex Assembly in Arabidopsis, THE PLANT CELL ONLINE, vol.21, issue.2, pp.460-478, 2009.
DOI : 10.1105/tpc.108.064444

H. C. Yen, C. Espiritu, C. , and E. C. , Rpn5 Is a Conserved Proteasome Subunit and Required for Proper Proteasome Localization and Assembly, Journal of Biological Chemistry, vol.11, issue.33, pp.30669-30676, 2003.
DOI : 10.1038/nature724

S. R. Collins, K. M. Miller, N. L. Maas, A. Roguev, J. Fillingham et al., Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map, Nature, vol.304, issue.7137, pp.806-810, 2007.
DOI : 10.1038/nature05649

V. Maytal-kivity, E. Pick, R. Piran, K. Hofmann, and M. H. Glickman, The COP9 signalosome-like complex in S. cerevisiae and links to other PCI complexes, The International Journal of Biochemistry & Cell Biology, vol.35, issue.5, pp.706-715, 2003.
DOI : 10.1016/S1357-2725(02)00378-3

N. Huang, I. Lee, E. M. Marcotte, and M. E. Hurles, Characterising and Predicting Haploinsufficiency in the Human Genome, PLoS Genetics, vol.16, issue.10, 2010.
DOI : 10.1371/journal.pgen.1001154.s021

M. Lek, K. J. Karczewski, E. V. Minikel, K. E. Samocha, E. Banks et al., Analysis of protein-coding genetic variation in 60,706 humans, Nature, vol.32, issue.7616, pp.285-291, 2016.
DOI : 10.1038/nbt.2835
URL : http://www.nature.com/nature/journal/v536/n7616/pdf/nature19057.pdf

H. M. Kim, Y. Yu, and Y. Cheng, Structure characterization of the 26S proteasome, Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, vol.1809, issue.2, pp.67-79, 2011.
DOI : 10.1016/j.bbagrm.2010.08.008

Z. Yu, O. Kleifeld, A. Lande-atir, M. Bsoul, M. Kleiman et al., Dual function of Rpn5 in two PCI complexes, the 26S proteasome and COP9 signalosome, Molecular Biology of the Cell, vol.105, issue.7, pp.911-920, 2011.
DOI : 10.1073/pnas.0801313105

L. Z. Peters, O. Karmon, G. David-kadoch, R. Hazan, T. Yu et al., The Protein Quality Control Machinery Regulates Its Misassembled Proteasome Subunits, PLOS Genetics, vol.154, issue.4, 2015.
DOI : 10.1371/journal.pgen.1005178.s004

F. Ebstein, A. Lehmann, and P. M. Kloetzel, The FAT10- and ubiquitin-dependent degradation machineries exhibit common and distinct requirements for MHC class I antigen presentation, Cellular and Molecular Life Sciences, vol.35, issue.7, pp.2443-2454, 2012.
DOI : 10.1042/CBI20100772
URL : https://link.springer.com/content/pdf/10.1007%2Fs00018-012-0933-5.pdf

I. Bochmann, F. Ebstein, A. Lehmann, J. Wohlschlaeger, S. U. Sixt et al., T lymphocytes export proteasomes by way of microparticles: a possible mechanism for generation of extracellular proteasomes, Journal of Cellular and Molecular Medicine, vol.47, issue.1, 2014.
DOI : 10.1093/rheumatology/ken042

, J. Cell. Mol. Med, vol.18, pp.59-68

U. Seifert, L. P. Bialy, F. Ebstein, D. Bech-otschir, A. Voigt et al., Immunoproteasomes Preserve Protein Homeostasis upon Interferon-Induced Oxidative Stress, Cell, vol.142, issue.4, pp.613-624, 2010.
DOI : 10.1016/j.cell.2010.07.036

C. M. Dambacher, E. J. Worden, M. A. Herzik, A. Martin, and G. C. Lander, Author response, eLife, vol.419, 2016.
DOI : 10.7554/eLife.13027.026

J. Boehringer, C. Riedinger, K. Paraskevopoulos, E. O. Johnson, E. D. Lowe et al., Structural and functional characterization of Rpn12 identifies residues required for Rpn10 proteasome incorporation, Biochemical Journal, vol.11, issue.1, pp.55-65, 2012.
DOI : 10.1074/jbc.271.10.5704

N. A. Bolar, C. Golzio, M. Zivná, G. Hayot, C. Van-hemelrijk et al., Heterozygous Loss-of-Function SEC61A1 Mutations Cause Autosomal-Dominant Tubulo-Interstitial and Glomerulocystic Kidney Disease with Anemia, The American Journal of Human Genetics, vol.99, issue.1, 2016.
DOI : 10.1016/j.ajhg.2016.05.028

, Am. J. Hum. Genet, vol.99, pp.174-187

G. Borck, F. Hög, M. L. Dentici, P. L. Tan, N. Sowada et al., , 2015.

, Genome Res, vol.25, pp.155-166

A. Dauber, C. Golzio, C. Guenot, F. M. Jodelka, M. Kibaek et al., SCRIB and PUF60 Are Primary Drivers of the Multisystemic Phenotypes of the 8q24.3 Copy-Number Variant, The American Journal of Human Genetics, vol.93, issue.5, pp.798-811, 2013.
DOI : 10.1016/j.ajhg.2013.09.010
URL : https://hal.archives-ouvertes.fr/hal-01707379

C. T. Gordon, K. N. Weaver, R. M. Zechi-ceide, E. C. Madsen, A. L. Tavares et al., Mutations in the Endothelin Receptor Type A Cause Mandibulofacial Dysostosis with Alopecia, The American Journal of Human Genetics, vol.96, issue.4, pp.519-531, 2015.
DOI : 10.1016/j.ajhg.2015.01.015

M. Isrie, M. Breuss, G. Tian, A. H. Hansen, F. Cristofoli et al.,

C. M. Dapena and E. P. , Mutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type, Am, 2015.

, J. Hum. Genet, vol.97, pp.790-800

E. Kague, M. Gallagher, S. Burke, M. Parsons, T. Franz-odendaal et al., Skeletogenic Fate of Zebrafish Cranial and Trunk Neural Crest, PLoS ONE, vol.79, issue.11, p.47394, 2012.
DOI : 10.1371/journal.pone.0047394.s001

C. Pardo-martin, A. Allalou, J. Medina, P. M. Eimon, C. Wählby et al., High-throughput hyperdimensional vertebrate phenotyping, Nature Communications, vol.233, issue.1, 1467.
DOI : 10.1006/dbio.2001.0201

M. Bartnik, B. Nowakowska, K. Derwi-nska, B. Wi-sniowiecka-kowalnik, M. Ke-?dzior et al., Application of array comparative genomic hybridization in 256 patients with developmental delay or intellectual disability, Journal of Applied Genetics, vol.461, issue.1, pp.125-144, 2014.
DOI : 10.1038/nature08490

S. Vergult, A. Dauber, B. Delle-chiaie, E. Van-oudenhove, M. Simon et al., 17q24.2 microdeletions: a new syndromal entity with intellectual disability, truncal obesity, mood swings and hallucinations, European Journal of Human Genetics, vol.43, issue.5, pp.534-539, 2012.
DOI : 10.1074/jbc.270.43.25526

E. M. Cooper, C. Cutcliffe, T. Z. Kristiansen, A. Pandey, C. M. Pickart et al., K63-specific deubiquitination by two JAMM/MPN+ complexes: BRISC-associated Brcc36 and proteasomal Poh1, The EMBO Journal, vol.15, issue.6, pp.621-631, 2009.
DOI : 10.1016/j.molcel.2007.07.024

J. H. Notwell, W. E. Heavner, S. F. Darbandi, S. Katzman, W. L. Mckenna et al., TBR1 regulates autism risk genes in the developing neocortex, TBR1 regulates autism risk genes in the developing neocortex, pp.1013-1022, 2016.
DOI : 10.1101/gr.203612.115

L. C. Burrage, T. N. Eble, P. M. Hixson, E. K. Roney, S. W. Cheung et al., American Journal of Medical Genetics Part A, vol.419, issue.4, pp.841-844, 2013.
DOI : 10.1038/nature01071

J. Blake, A. Riddell, S. Theiss, A. P. Gonzalez, B. Haase et al., Sequencing of a Patient with Balanced Chromosome Abnormalities and Neurodevelopmental Disease Identifies Disruption of Multiple High Risk Loci by Structural Variation, PLoS ONE, vol.4, issue.3, p.90894, 2014.
DOI : 10.1371/journal.pone.0090894.s004

R. Verma, L. Aravind, R. Oania, W. H. Mcdonald, J. R. Yates et al., Role of Rpn11 Metalloprotease in Deubiquitination and Degradation by the 26S Proteasome, Science, vol.298, issue.5593, pp.611-615, 2002.
DOI : 10.1126/science.1075898

J. De-ligt, M. H. Willemsen, B. W. Van-bon, T. Kleefstra, H. G. Yntema et al., Diagnostic Exome Sequencing in Persons with Severe Intellectual Disability, New England Journal of Medicine, vol.367, issue.20, pp.1921-1929, 2012.
DOI : 10.1056/NEJMoa1206524