Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology
Open accessAbstract
Mutations in SQSTM1 encoding the sequestosome 1/p62 protein have recently been identified in familial and sporadic cases of amyotrophic lateral sclerosis (ALS). p62 is a component of the ubiquitin inclusions detected in degenerating neurons in ALS patients. We sequenced SQSTM1 in 90 French patients with familial ALS (FALS) and 74 autopsied ALS cases with sporadic ALS (SALS). We identified, at the heterozygote state, one missense c.1175C>T, p.Pro392Leu (exon 8) in one of our FALS and one substitution in intron 7 (the c.1165+1G>A, previously called IVS7+1 G-A, A390X) affecting the exon 7 splicing site in one SALS. These mutations that are located in the ubiquitin-associated domain (UBA domain) of the p62 protein have already been described in Paget's disease and ALS patients carrying these mutations had both concomitant Paget's disease. However, we also identified two novel missense mutations in two SALS: the c.259A>G, p.Met87Val in exon 2 and the c.304A>G, p.Lys102Glu in exon 3. These mutations that were not detected in 360 control subjects are possibly pathogenic. Neuropathology analysis of three patients carrying SQSTM1 variants revealed the presence of large round p62 inclusions in motor neurons, and immunoblot analysis showed an increased p62 and TDP-43 protein levels in the spinal cord. Our results confirm that SQSTM1 gene mutations could be the cause or genetic susceptibility factor of ALS in some patients.
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SQSTM1 mutations are a rare cause of ALS-FTD, accounting for ~1-3.5% of cases with or without family history, and also cause Paget's disease of bone and inclusion body myositis.
“SQSTM1 mutations are not only a rare cause of ALS-FTD, accounting for ~1-3.5% of cases with or without family history [123–125], but also Paget’s disease of bone (PDB), a chronic and progressive skeletal disorder characterized by disorganized bone turnover [126,127], and inclusion body myositis (IBM) [128].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [125]
ALS-FTD-associated SQSTM1 mutations frequently affect the UBA and LIR domains involved in autophagy and include both missense and nonsense mutations.
“ALS-FTD-associated SQSTM1 mutations frequently affect the UBA and LIR domains involved in autophagy and include both missense and nonsense mutations [123–125].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [125]
SQSTM1 mutations affect muscle, bone, and liver.
“SQSTM1 mutations affect muscle, bone, and liver [125,367,368]”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [125]
Cites
Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., Bruce, J., Schuck, T., Grossman, M., Clark, C. M., et al. (2006) · Science · doi:10.1126/science.1134108 · Cited by 6,576 · see citing works
El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis
Brooks, B. R., Miller, R. G., Swash, M., & Munsat, T. L. (2000) · Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders · doi:10.1080/146608200300079536 · Cited by 5,433 · see citing works
DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., Nicholson, A. M., Finch, N. A., Flynn, H., Adamson, J., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.011 · Cited by 4,936 · see citing works
A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD
Renton, A. E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J. R., Schymick, J. C., Laaksovirta, H., van Swieten, J. C., Myllykangas, L., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.010 · Cited by 4,409 · see citing works
Watts, G. D. J., Wymer, J., Kovach, M. J., Mehta, S. G., Mumm, S., Darvish, D., Pestronk, A., Whyte, M. P., & Kimonis, V. E. (2004) · Nature Genetics · doi:10.1038/ng1332 · Cited by 1,391 · see citing works
Mutations of optineurin in amyotrophic lateral sclerosis
Maruyama, H., Morino, H., Ito, H., Izumi, Y., Kato, H., Watanabe, Y., Kinoshita, Y., Kamada, M., Nodera, H., Suzuki, H., et al. (2010) · Nature · doi:10.1038/nature08971 · Cited by 1,265 · see citing works
Exome Sequencing Reveals VCP Mutations as a Cause of Familial ALS
Johnson, J. O., Mandrioli, J., Benatar, M., Abramzon, Y., Van Deerlin, V. M., Trojanowski, J. Q., Gibbs, J. R., Brunetti, M., Gronka, S., Wuu, J., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.11.036 · Cited by 1,235 · see citing works
A harmonized classification system for FTLD-TDP pathology
Mackenzie, I. R., Neumann, M., Baborie, A., Sampathu, D. M., du Plessis, D., Jaros, E., Perry, R. H., Trojanowski, J. Q., Mann, D. M. A., & Lee, V. M. ‐. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0845-8 · Cited by 1,013 · see citing works
Mackenzie, I. R. A., Bigio, E. H., Ince, P. G., Geser, F., Neumann, M., Cairns, N. J., Kwong, L. K., Forman, M. S., Ravits, J., Stewart, H., et al. (2007) · Annals of Neurology · doi:10.1002/ana.21147 · Cited by 992 · see citing works
Fecto, F. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.250 · Cited by 650 · see citing works
Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone.
Laurin, N., Brown, J. P., Morissette, J., & Raymond, V. (2002) · The American Journal of Human Genetics · doi:10.1086/340731 · Cited by 563 · see citing works
Al-Sarraj, S., King, A., Troakes, C., Smith, B., Maekawa, S., Bodi, I., Rogelj, B., Al-Chalabi, A., Hortobágyi, T., & Shaw, C. E. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0911-2 · Cited by 475 · see citing works
Dai, R. M., & Li, C.-C. H. (2001) · Nature Cell Biology · doi:10.1038/35087056 · Cited by 437 · see citing works
Domain-specific mutations in sequestosome 1 (SQSTM1) cause familial and sporadic Paget’s disease.
Hocking, L. J. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.22.2735 · Cited by 350 · see citing works
Kuusisto, E., Salminen, A., & Alafuzoff, I. I. (2001) · Neuroreport · doi:10.1097/00001756-200107200-00009 · Cited by 347 · see citing works
Millecamps, S., Salachas, F., Cazeneuve, C., Gordon, P., Bricka, B., Camuzat, A., Guillot‐Noël, L., Russaouen, O., Bruneteau, G., Pradat, P., et al. (2010) · Journal of Medical Genetics · doi:10.1136/jmg.2010.077180 · Cited by 308 · see citing works
Self-citationVadlamudi, R. K., Joung, I., Strominger, J. L., & Shin, J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.34.20235 · Cited by 299 · see citing works
<i>SQSTM1</i> mutations in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
Rubino, E., Rainero, I., Chiò, A., Rogaeva, E., Galimberti, D., Fenoglio, P., Grinberg, Y., Isaia, G., Calvo, A., Gentile, S., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e31826e25df · Cited by 286 · see citing works
Albagha, O., Visconti, M. R., Alonso, N., Langston, A. L., Cundy, T., Dargie, R., Dunlop, M. G., Fraser, W. D., Hooper, M. J., Isaia, G., et al. (2010) · Nature Genetics · doi:10.1038/ng.562 · Cited by 280 · see citing works
Genetic inactivation of p62 leads to accumulation of hyperphosphorylated tau and neurodegeneration
Ramesh Babu, J., Lamar Seibenhener, M., Peng, J., Strom, A., Kemppainen, R., Cox, N., Zhu, H., Wooten, M. C., Diaz‐Meco, M. T., Moscat, J., et al. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05340.x · Cited by 258 · see citing works
The Epidemiology of Paget's Disease in Britain: Is the Prevalence Decreasing?
Cooper, C. C., Schafheutle, K., Dennison, E., et al. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.2.192 · Cited by 245 · see citing works
Brady, O. A., Meng, P., Zheng, Y., Mao, Y., & Hu, F. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07098.x · Cited by 215 · see citing works
Brettschneider, J., Deerlin, V. M. V., Robinson, J. L., Kwong, L. K., Lee, E. B., Ali, Y., Safren, N., Monteiro, M. J., Toledo, J. B., Elman, L. B., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-0970-z · Cited by 183 · see citing works
Millecamps, S., Boillée, S., Ber, I. L., Seilhean, D., Teyssou, E., Giraudeau, M., Moigneu, C., Vandenberghe, N., Danel-Brunaud, V., Corcia, P., et al. (2012) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2011-100699 · Cited by 179 · see citing works
Self-citationGleason, C. E., Ordureau, A., Gourlay, R., Arthur, J. S. C., & Cohen, P. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.267567 · Cited by 173 · see citing works
Mizuno, Y., Amari, M., Takatama, M., Aizawa, H., Mihara, B., & Okamoto, K. (2006) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2006.05.060 · Cited by 158 · see citing works
Brettschneider, J., Libon, D. J., Toledo, J. B., Xie, S. X., McCluskey, L. F., Elman, L. B., Geser, F., Lee, V. M. ‐., Grossman, M., & Trojanowski, J. Q. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0932-x · Cited by 140 · see citing works
Daroszewska, A., van 't Hof, R. J., Rojas, J. A., Layfield, R., Landao-Basonga, E., Rose, L., Rose, K., & Ralston, S. H. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr172 · Cited by 131 · see citing works
Bunina bodies in amyotrophic lateral sclerosis immunostained with rabbit anti-cystatin C serum
Okamoto, K., Hirai, S., Amari, M., Watanabe, M., & Sakurai, A. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90576-7 · Cited by 127 · see citing works
Geser, F., Robinson, J. L., Malunda, J. A., Xie, S. X., Clark, C. M., Kwong, L. K., Moberg, P. J., Moore, E. M., Deerlin, V. M. V., Lee, V. M. ‐., et al. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.254 · Cited by 106 · see citing works
Screening of OPTN in French familial amyotrophic lateral sclerosis
Millecamps, S., Boillée, S., Chabrol, E., Camu, W., Cazeneuve, C., Salachas, F., Pradat, P., Danel-Brunaud, V., Vandenberghe, N., Corcia, P., et al. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.11.005 · Cited by 84 · see citing works
Self-citationPikkarainen, M., Hartikainen, P. H., & Alafuzoff, I. I. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31816a1da2 · Cited by 82 · see citing works
Mutations in the gene encoding p62 in Japanese patients with amyotrophic lateral sclerosis
Hirano, M., Nakamura, Y., Saigoh, K., Sakamoto, H., Ueno, S., Isono, C., Miyamoto, K., Akamatsu, M., Mitsui, Y., & Kusunoki, S. (2013) · Neurology · doi:10.1212/wnl.0b013e31827f0fe5 · Cited by 81 · see citing works
Collet, C., Michou, L., Audran, M., Chasseigneaux, S., Hilliquin, P., Bardin, T., Lemaire, I., Cornélis, F., Launay, J., Orcel, P., et al. (2006) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.061106 · Cited by 78 · see citing works
Cavey, J. R., Ralston, S. H., Sheppard, P. W., Ciani, B., Gallagher, T. R. A., Long, J., Searle, M. S., & Layfield, R. (2006) · Calcified Tissue International · doi:10.1007/s00223-005-1299-6 · Cited by 76 · see citing works
Tanji, K., Zhang, H., Mori, F., Kakita, A., Takahashi, H., & Wakabayashi, K. (2012) · Journal of Neuroscience Research · doi:10.1002/jnr.23081 · Cited by 70 · see citing works
Recent advances in understanding the molecular basis of Paget disease of bone
Goode, A., & Layfield, R. (2009) · Journal of Clinical Pathology · doi:10.1136/jcp.2009.064428 · Cited by 68 · see citing works
Motor neuron disease clinically limited to the lower motor neuron is a diffuse TDP-43 proteinopathy
Geser, F., Stein, B., Partain, M., Elman, L. B., McCluskey, L. F., Xie, S. X., Deerlin, V. M. V., Kwong, L. K., Lee, V. M. ‐., & Trojanowski, J. Q. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0797-z · Cited by 61 · see citing works
Genetics of Paget’s disease of bone
Michou, L., Collet, C., Laplanche, J., Orcel, P., & Cornélis, F. (2006) · Joint Bone Spine · doi:10.1016/j.jbspin.2005.05.009 · Cited by 49 · see citing works
On Behalf of the GenePage Project, Falchetti, A., Stefano, M. D., Marini, F., Ortolani, S., Ulivieri, F. M., Bergui, S., Masi, L., Cepollaro, C., Benucci, M., et al. (2008) · Calcified Tissue International · doi:10.1007/s00223-008-9192-8 · Cited by 48 · see citing works
Sequestosome 1/p62: across diseases
Geetha, T., Viswaprakash, N., Sycheva, M., & Babu, J. R. (2012) · Biomarkers · doi:10.3109/1354750x.2011.653986 · Cited by 45 · see citing works
Distinct TDP-43 pathology in ALS patients with ataxin 2 intermediate-length polyQ expansions
Hart, M. P., Brettschneider, J., Lee, V. M. ‐., Trojanowski, J. Q., & Gitler, A. D. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-0985-5 · Cited by 42 · see citing works
Mutations in UBQLN2 are rare in French amyotrophic lateral sclerosis
Millecamps, S., Corcia, P., Cazeneuve, C., Boillée, S., Seilhean, D., Danel-Brunaud, V., Vandenberghe, N., Pradat, P.-F., Le Forestier, N., Lacomblez, L., et al. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.11.010 · Cited by 40 · see citing works
Self-citationEpidemiogenetic study of French families with Paget's disease of bone
Michou, L., Collet, C., Morissette, J., Audran, M., Thomas, T., Gagnon, É., Launay, J., Laplanche, J., Brown, J. P., & Orcel, P. (2011) · Joint Bone Spine · doi:10.1016/j.jbspin.2011.07.005 · Cited by 36 · see citing works
Lain, A. H., Millecamps, S., Dubourg, O., et al. (2010) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2010.208868 · Cited by 28 · see citing works
Self-citationQuestioning on the role of D amino acid oxidase in familial amyotrophic lateral sclerosis
Millecamps, S., da Barroca, S., Cazeneuve, C., Salachas, F., Pradat, P., Danel-Brunaud, V., Vandenberghe, N., Lacomblez, L., Forestier, N. L., Bruneteau, G., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006190107 · Cited by 21 · see citing works
Self-citationClinical Features and Pharmacologic Treatment of Paget’s Disease
Hamdy, R. C. (1995) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(18)30047-1 · Cited by 14 · see citing works
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“neural tissues manifest the detrimental effects of compromised autophagy [11], but to varying extents [365,366]: SQSTM1 mutations affect muscle, bone, and liver [125,367,368]; C9orf72 deficiency leads to lymphocytic inflammation, lymphadenopathy, and splenomegaly [149]; CHMP2B mutations induce oligodendroglial patholo…”
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- Authors
- Teyssou, E., Takeda, T., Lebon, V., Boillée, S., Doukouré, B., Bataillon, G., Sazdovitch, V., Cazeneuve, C., Meininger, V., LeGuern, E., Salachas, F., Seilhean, D., & Millecamps, S.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Pitié-Salpêtrière Hospital (FR)
- Corresponding author
- Millecamps, Stéphanie
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2013-02-17
- Volume
- 125
- Issue
- 4
- Pages
- 511-522
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2151616372
- Cited by
- 241
- References
- 47
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 8 · 2023: 18 · 2022: 16 · 2021: 18 · 2020: 30 · 2019: 16 · 2018: 22 · 2017: 19 · 2016: 22 · 2015: 21 · 2014: 15 · 2013: 13
- FWCI
- 15.02
- Type
- journal article
- Language
- en
- Open access
- green
- hal.science
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Keywords
- p62, amyotrophic lateral sclerosis, familial ALS, sporadic ALS, missense mutations, UBA domain, TDP-43, motor neurons, neuropathology, genetic susceptibility, Paget's disease
- MeSH terms
- Sequestosome-1 Protein, Adult, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Brain, DNA-Binding Proteins, Female, Heterozygote, Humans, Male, Middle Aged, Mutation, Ubiquitin, Adaptor Proteins, Signal Transducing
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