{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:42:23Z","timestamp":1790516543337,"version":"4.1.0"},"reference-count":152,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T00:00:00Z","timestamp":1595980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Spinal muscular atrophy (SMA) is currently classified into five different subtypes, from the most severe (type 0) to the mildest (type 4) depending on age at onset, best motor function achieved, and copy number of the SMN2 gene. The two recent approved treatments for SMA patients revolutionized their life quality and perspectives. However, upon treatment with Nusinersen, the most widely administered therapy up to date, a high degree of variability in therapeutic response was observed in adult SMA patients. These data, together with the lack of natural history information and the wide spectrum of disease phenotypes, suggest that further efforts are needed to develop precision medicine approaches for all SMA patients. Here, we compile the current methods for functional evaluation of adult SMA patients treated with Nusinersen. We also present an overview of the known molecular changes underpinning disease heterogeneity. We finally highlight the need for novel techniques, i.e., -omics approaches, to capture phenotypic differences and to understand the biological signature in order to revise the disease classification and device personalized treatments.<\/jats:p>","DOI":"10.3390\/jpm10030075","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T07:31:45Z","timestamp":1596007905000},"page":"75","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["The Identification of Novel Biomarkers Is Required to Improve Adult SMA Patient Stratification, Diagnosis and Treatment"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3430-6839","authenticated-orcid":false,"given":"Piera","family":"Smeriglio","sequence":"first","affiliation":[{"name":"Centre of Research in Myology, Institute of Myology, Sorbonne Universit\u00e9, INSERM, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6600-8572","authenticated-orcid":false,"given":"Paul","family":"Langard","sequence":"additional","affiliation":[{"name":"Centre of Research in Myology, Institute of Myology, Sorbonne Universit\u00e9, INSERM, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6938-6368","authenticated-orcid":false,"given":"Giorgia","family":"Querin","sequence":"additional","affiliation":[{"name":"Centre of Research in Myology, Institute of Myology, Sorbonne Universit\u00e9, INSERM, 75013 Paris, France"},{"name":"Association Institut de Myologie, Plateforme Essais Cliniques Adultes, 75013 Paris, France"},{"name":"APHP, Service de Neuromyologie, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3722-4529","authenticated-orcid":false,"given":"Maria Grazia","family":"Biferi","sequence":"additional","affiliation":[{"name":"Centre of Research in Myology, Institute of Myology, Sorbonne Universit\u00e9, INSERM, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy-determining gene","volume":"80","author":"Lefebvre","year":"1995","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1097\/GIM.0b013e3181c5e713","article-title":"Perspectives and diagnostic considerations in spinal muscular atrophy","volume":"12","author":"Prior","year":"2010","journal-title":"Genet. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"339","DOI":"10.2174\/1389202919666180101154916","article-title":"Molecular factors involved in spinal muscular atrophy pathways as possible disease-modifying candidates","volume":"19","author":"Maretina","year":"2018","journal-title":"Curr. Genom."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Lunn, M.R., and Wang, C.H. (2008). Spinal muscular atrophy. Lancet.","DOI":"10.1016\/S0140-6736(08)60921-6"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00415-005-0912-y","article-title":"SMN2 copy number predicts acute or chronic spinal muscular atrophy but does not account for intrafamilial variability in siblings","volume":"253","author":"Illa","year":"2006","journal-title":"J. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3233\/JND-190399","article-title":"Spinal Muscular Atrophy (SMA) Subtype Concordance in Siblings: Findings From the Cure SMA Cohort","volume":"7","author":"Jones","year":"2020","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1086\/338627","article-title":"Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: Fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy","volume":"70","author":"Schwarzer","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1126\/science.1155085","article-title":"Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy","volume":"320","author":"Oprea","year":"2008","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.ajhg.2016.07.014","article-title":"The power of human protective modifiers: PLS3 and CORO1C unravel impaired endocytosis in spinal muscular atrophy and rescue SMA phenotype","volume":"99","author":"Hosseinibarkooie","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.ajhg.2017.01.005","article-title":"Neurocalcin delta suppression protects against spinal muscular atrophy in humans and across species by restoring impaired endocytosis","volume":"100","author":"Riessland","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.nmd.2018.01.003","article-title":"Correlation between SMA type and SMN2 copy number revisited: An analysis of 625 unrelated Spanish patients and a compilation of 2834 reported cases","volume":"28","author":"Calucho","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/j.celrep.2017.01.035","article-title":"Single-cell analysis of SMN reveals its broader role in neuromuscular disease","volume":"18","author":"Litterman","year":"2017","journal-title":"Cell Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.nbd.2017.01.011","article-title":"Spinal muscular atrophy: Factors that modulate motor neurone vulnerability","volume":"102","author":"Tu","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1056\/NEJMoa1702752","article-title":"Nusinersen versus sham control in infantile-onset spinal muscular atrophy","volume":"377","author":"Finkel","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1212\/WNL.0000000000002445","article-title":"Results from a phase 1 study of nusinersen (ISIS-SMNRx) in children with spinal muscular atrophy","volume":"86","author":"Chiriboga","year":"2016","journal-title":"Neurology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6501","DOI":"10.1021\/acs.jmedchem.8b00741","article-title":"Discovery of risdiplam, a selective survival of motor neuron-2 (SMN2) gene splicing modifier for the treatment of spinal muscular atrophy (SMA)","volume":"61","author":"Ratni","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1706198","article-title":"Single-dose gene-replacement therapy for spinal muscular atrophy","volume":"377","author":"Mendell","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"453","DOI":"10.3233\/JND-190416","article-title":"Safety and treatment effects of nusinersen in longstanding adult 5q-SMA type 3\u2014A prospective observational study","volume":"6","author":"Walter","year":"2019","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S1474-4422(20)30037-5","article-title":"Nusinersen in adults with 5q spinal muscular atrophy: A non-interventional, multicentre, observational cohort study","volume":"19","author":"Hagenacker","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1756286420907803","DOI":"10.1177\/1756286420907803","article-title":"Experiences from treating seven adult 5q spinal muscular atrophy patients with Nusinersen","volume":"13","author":"Jochmann","year":"2020","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1212\/01.wnl.0000324623.89105.c4","article-title":"Natural history of SMA IIIb: Muscle strength decreases in a predictable sequence and magnitude","volume":"71","author":"Deymeer","year":"2008","journal-title":"Neurology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/ejhg.2012.233","article-title":"Clinical and molecular cross-sectional study of a cohort of adult type III spinal muscular atrophy patients: Clues from a biomarker study","volume":"21","author":"Tiziano","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fneur.2019.00898","article-title":"Biomarkers and the development of a personalized medicine approach in spinal muscular atrophy","volume":"10","author":"Kariyawasam","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/ene.13534","article-title":"Muscle strength and motor function throughout life in a cross-sectional cohort of 180 patients with spinal muscular atrophy types 1c\u20134","volume":"25","author":"Wadman","year":"2018","journal-title":"Eur. J. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13023-020-01367-y","article-title":"Natural history of lung function in spinal muscular atrophy","volume":"15","author":"Wijngaarde","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.nmd.2007.05.009","article-title":"An expanded version of the Hammersmith Functional Motor Scale for SMA II and III patients","volume":"17","author":"Glanzman","year":"2007","journal-title":"Neuromuscul. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1212\/WNL.0b013e318271f7e4","article-title":"Prospective cohort study of spinal muscular atrophy types 2 and 3","volume":"79","author":"Kaufmann","year":"2012","journal-title":"Neurology"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Montes, J., McDermott, M.P., Mirek, E., Mazzone, E.S., Main, M., Glanzman, A.M., Duong, T., Young, S.D., Salazar, R., and Pasternak, A. (2018). Ambulatory function in spinal muscular atrophy: Age-related patterns of progression. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199657"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Faravelli, I., Meneri, M., Saccomanno, D., Velardo, D., Abati, E., Gagliardi, D., Parente, V., Petrozzi, L., Ronchi, D., and Stocchetti, N. (2020). Nusinersen treatment and cerebrospinal fluid neurofilaments: An explorative study on Spinal Muscular Atrophy type 3 patients. J. Cell. Mol. Med., 1\u20136.","DOI":"10.1111\/jcmm.14939"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kessler, T., Latzer, P., Schmid, D., Warnken, U., Saffari, A., Ziegler, A., Kollmer, J., M\u00f6hlenbruch, M., Ulfert, C., and Herweh, C. (2020). Cerebrospinal fluid proteomic profiling in nusinersen-treated patients with spinal muscular atrophy. J. Neurochem., e14953.","DOI":"10.1111\/jnc.14953"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1002\/mus.24670","article-title":"Spinal muscular atrophy functional composite score: A functional measure in spinal muscular atrophy","volume":"52","author":"Montes","year":"2015","journal-title":"Muscle Nerve"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.nmd.2011.02.014","article-title":"Assessing upper limb function in nonambulant SMA patients: Development of a new module","volume":"21","author":"Mazzone","year":"2011","journal-title":"Neuromuscul. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1002\/mus.25430","article-title":"Revised upper limb module for spinal muscular atrophy: Development of a new module","volume":"55","author":"Mazzone","year":"2017","journal-title":"Muscle Nerve"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1002\/mus.26419","article-title":"Revised upper limb module for spinal muscular atrophy: 12 month changes","volume":"59","author":"Pera","year":"2019","journal-title":"Muscle Nerve"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.3389\/fneur.2019.01166","article-title":"Clinical implication of dosimetry of computed tomography-and fluoroscopy-guided intrathecal therapy with nusinersen in adult patients with spinal muscular atrophy","volume":"10","author":"Kizina","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1756286418803246","DOI":"10.1177\/1756286418803246","article-title":"Feasibility and safety of intrathecal treatment with nusinersen in adult patients with spinal muscular atrophy","volume":"11","author":"Stolte","year":"2018","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0022-510X(96)00284-5","article-title":"A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients","volume":"146","author":"Zerres","year":"1997","journal-title":"J. Neurol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"(2002). ATS statement: Guidelines for the six-minute walk test. Am. J. Respir. Crit. Care Med., 166, 111\u2013117.","DOI":"10.1164\/ajrccm.166.1.at1102"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1002\/mus.25120","article-title":"Six-minute walk test is reliable and valid in spinal muscular atrophy","volume":"54","author":"Montes","year":"2016","journal-title":"Muscle Nerve"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1212\/WNL.0000000000003847","article-title":"Reference values for developing responsive functional outcome measures across the lifespan","volume":"88","author":"McKay","year":"2017","journal-title":"Neurology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"ii32","DOI":"10.1136\/jnnp.2005.069211","article-title":"The basics of electromyography","volume":"76","author":"Mills","year":"2005","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S1567-4231(04)04012-2","article-title":"Peripheral nerve conduction studies and neuromuscular junction testing","volume":"Volume 4","author":"Kimura","year":"2004","journal-title":"Handbook of Clinical Neurophysiology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1002\/acn3.23","article-title":"Electrophysiological biomarkers in spinal muscular atrophy: Proof of concept","volume":"1","author":"Arnold","year":"2014","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1109\/TBME.2004.834281","article-title":"Motor unit number index (MUNIX)","volume":"51","author":"Nandedkar","year":"2004","journal-title":"IEEE Tans. Biomed. Eng."},{"key":"ref_45","first-page":"187","article-title":"Role of electromyography in the diagnosis of motor neuron disorders","volume":"30","year":"1992","journal-title":"Neuropatol. Pol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1002\/ana.25101","article-title":"Natural history of infantile-onset spinal muscular atrophy","volume":"82","author":"Kolb","year":"2017","journal-title":"Ann. Neurol."},{"key":"ref_47","first-page":"704","article-title":"Natural history of denervation in SMA: Relation to age, SMN2 copy number, and function","volume":"57","author":"Swoboda","year":"2005","journal-title":"Ann. Neurol. Offi. J. Am. Neurol. Assoc. Child Neurol. Soc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1016\/j.clinph.2018.08.025","article-title":"The motor unit number index (MUNIX) profile of patients with adult spinal muscular atrophy","volume":"129","author":"Querin","year":"2018","journal-title":"Clini. Neurophysiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"101618","DOI":"10.1016\/j.nicl.2018.101618","article-title":"The spinal and cerebral profile of adult spinal-muscular atrophy: A multimodal imaging study","volume":"21","author":"Querin","year":"2019","journal-title":"NeuroImage Clin."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s10334-013-0403-6","article-title":"Construction of an in vivo human spinal cord atlas based on high-resolution MR images at cervical and thoracic levels: Preliminary results","volume":"27","author":"Taso","year":"2014","journal-title":"Magn. Reson. Mater. Phys. Biol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/ng0797-265","article-title":"Correlation between severity and SMN protein level in spinal muscular atrophy","volume":"16","author":"Lefebvre","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/1753","article-title":"Identification of a candidate modifying gene for spinal muscular atrophy by comparative genomics","volume":"20","author":"Scharf","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1097\/00019052-200310000-00005","article-title":"Spinal muscular atrophies reveal motor neuron vulnerability to defects in ribonucleoprotein handling","volume":"16","author":"Anderson","year":"2003","journal-title":"Curr. Opin. Neurol."},{"key":"ref_54","first-page":"72","article-title":"The gene encoding p44, a subunit of the transcription factor TFIIH, is involved in large-scale deletions associated with Werdnig-Hoffmann disease","volume":"60","author":"Seroz","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Jiang, J., Huang, J., Gu, J., Cai, X., Zhao, H., and Lu, H. (2019). Genomic analysis of a spinal muscular atrophy (SMA) discordant family identifies a novel mutation in TLL2, an activator of growth differentiation factor 8 (myostatin): A case report. BMC Med. Genet., 20.","DOI":"10.1186\/s12881-019-0935-3"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/S0140-6736(95)90732-7","article-title":"PCR-based DNA test to confirm clinical diagnosis of autosomal recessive spinal muscular atrophy","volume":"345","author":"Grootscholten","year":"1995","journal-title":"Lancet"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1093\/hmg\/6.8.1205","article-title":"The survival motor neuron protein in spinal muscular atrophy","volume":"6","author":"Coovert","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1086\/515465","article-title":"Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNT and SMNC gene copy number","volume":"60","author":"McAndrew","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/sj.ejhg.5200210","article-title":"Correlation of SMN t and SMN c gene copy number with age of onset and survival in spinal muscular atrophy","volume":"6","author":"Taylor","year":"1998","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1097\/00125817-200201000-00004","article-title":"Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2","volume":"4","author":"Mailman","year":"2002","journal-title":"Genet. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/humu.10221","article-title":"Determination of SMN1 and SMN2 copy number using TaqMan\u2122 technology","volume":"22","author":"Anhuf","year":"2003","journal-title":"Hum. Mutat."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s10048-006-0051-3","article-title":"Spinal muscular atrophy genotyping by gene dosage using multiple ligation-dependent probe amplification","volume":"7","author":"Scarciolla","year":"2006","journal-title":"Neurogenetics"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1007\/s00439-006-0156-7","article-title":"Mildly affected patients with spinal muscular atrophy are partially protected by an increased SMN2 copy number","volume":"119","author":"Wirth","year":"2006","journal-title":"Hum. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s10048-007-0093-1","article-title":"Robust quantification of the SMN gene copy number by real-time TaqMan PCR","volume":"8","author":"Robinson","year":"2007","journal-title":"Neurogenetics"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1097\/GIM.0b013e31803d35bc","article-title":"Copy number analysis of survival motor neuron genes by multiplex ligation-dependent probe amplification","volume":"9","author":"Huang","year":"2007","journal-title":"Genet. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.nmd.2007.02.006","article-title":"The Hammersmith functional score correlates with the SMN2 copy number: A multicentric study","volume":"17","author":"Tiziano","year":"2007","journal-title":"Neuromuscul. Disord."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1002\/mus.21350","article-title":"An analysis of disease severity based on SMN2 copy number in adults with spinal muscular atrophy","volume":"40","author":"Elsheikh","year":"2009","journal-title":"Muscle Nerve Off. J. Am. Assoc. Electrodiagn. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1089\/gtmb.2010.0253","article-title":"Accuracy of marker analysis, quantitative real-time polymerase chain reaction, and multiple ligation-dependent probe amplification to determine SMN2 copy number in patients with spinal muscular atrophy","volume":"15","author":"Alias","year":"2011","journal-title":"Genet. Test. Mol. Biomark."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ejpn.2011.07.007","article-title":"Correlation of SMN2, NAIP, p44, H4F5 and Occludin genes copy number with spinal muscular atrophy phenotype in Tunisian patients","volume":"16","author":"Amara","year":"2012","journal-title":"Eur. J. Paediatric Neurol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e33572","DOI":"10.1371\/journal.pone.0033572","article-title":"Evaluation of SMN protein, transcript, and copy number in the biomarkers for spinal muscular atrophy (BforSMA) clinical study","volume":"7","author":"Crawford","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1373\/clinchem.2012.183038","article-title":"Newborn screening for spinal muscular atrophy by calibrated short-amplicon melt profiling","volume":"58","author":"Dobrowolski","year":"2012","journal-title":"Clin. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/mgg3.10","article-title":"A homozygous double mutation in SMN 1: A complicated genetic diagnosis of SMA","volume":"1","author":"Kirwin","year":"2013","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/jhg.2015.104","article-title":"Joint effect of the SMN2 and SERF1A genes on childhood-onset types of spinal muscular atrophy in Serbian patients","volume":"60","author":"Romac","year":"2015","journal-title":"J. Hum. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Fang, P., Li, L., Zeng, J., Zhou, W.J., Wu, W.Q., Zhong, Z.Y., Yan, T.Z., Xie, J.S., Huang, J., and Lin, L. (2015). Molecular characterization and copy number of SMN1, SMN2 and NAIP in Chinese patients with spinal muscular atrophy and unrelated healthy controls. BMC Musculoskel. Disord., 16.","DOI":"10.1186\/s12891-015-0457-x"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1002\/mgg3.141","article-title":"SMN1 and SMN2 copy numbers in cell lines derived from patients with spinal muscular atrophy as measured by array digital PCR","volume":"3","author":"Stabley","year":"2015","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.ajhg.2009.08.002","article-title":"A positive modifier of spinal muscular atrophy in the SMN2 gene","volume":"85","author":"Prior","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1136\/jmg.2010.079004","article-title":"The c. 859G> C variant in the SMN2 gene is associated with types II and III SMA and originates from a common ancestor","volume":"47","author":"Bernal","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"E1110","DOI":"10.1002\/humu.21173","article-title":"A rare SMN2 variant in a previously unrecognized composite splicing regulatory element induces exon 7 inclusion and reduces the clinical severity of spinal muscular atrophy","volume":"31","author":"Vezain","year":"2010","journal-title":"Hum. Mutat."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1006\/geno.1994.1282","article-title":"A multicopy dinucleotide marker that maps close to the spinal muscular atrophy gene","volume":"21","author":"Burghes","year":"1994","journal-title":"Genomics"},{"key":"ref_80","first-page":"805","article-title":"Deletions of the survival motor neuron gene in unaffected siblings of patients with spinal muscular atrophy","volume":"57","author":"Cobben","year":"1995","journal-title":"Am. J. Hum. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1093\/hmg\/4.10.1927","article-title":"Molecular analysis of candidate genes on chromosome 5q13 in autosomal recessive spinal muscular atrophy: Evidence of homozygous deletions of the SMN gene in unaffected individuals","volume":"4","author":"Hahnen","year":"1995","journal-title":"Hum. Mol. Genet."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1093\/hmg\/dds540","article-title":"Plastin 3 ameliorates spinal muscular atrophy via delayed axon pruning and improves neuromuscular junction functionality","volume":"22","author":"Ackermann","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1007\/s00018-015-2084-y","article-title":"Plastin 3 is upregulated in iPSC-derived motoneurons from asymptomatic SMN1-deleted individuals","volume":"73","author":"Heesen","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1111\/j.1468-1331.2009.02693.x","article-title":"Carrier frequency of SMA by quantitative analysis of the SMN1 deletion in the Iranian population","volume":"17","author":"Hasanzad","year":"2010","journal-title":"Eur. J. Neurol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e89970","DOI":"10.1172\/jci.insight.89970","article-title":"Plastin-3 extends survival and reduces severity in mouse models of spinal muscular atrophy","volume":"2","author":"Kaifer","year":"2017","journal-title":"JCI Insight"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"McGovern, V.L., Massoni-Laporte, A., Wang, X., Le, T.T., Le, H.T., Beattie, C.E., Rich, M.M., and Burghes, A.H. (2015). Plastin 3 expression does not modify spinal muscular atrophy severity in the \u03947 SMA mouse. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132364"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5074","DOI":"10.1523\/JNEUROSCI.5808-11.2012","article-title":"Survival motor neuron affects plastin 3 protein levels leading to motor defects","volume":"32","author":"Hao","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1093\/brain\/awy167","article-title":"CHP1 reduction ameliorates spinal muscular atrophy pathology by restoring calcineurin activity and endocytosis","volume":"141","author":"Janzen","year":"2018","journal-title":"Brain"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.ajhg.2019.05.008","article-title":"NCALD Antisense oligonucleotide therapy in addition to nusinersen further ameliorates spinal muscular atrophy in mice","volume":"105","author":"Schneider","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s43042-019-0044-z","article-title":"Genetic pattern of SMN1, SMN2, and NAIP genes in prognosis of SMA patients","volume":"21","author":"Hassan","year":"2020","journal-title":"Egypt. J. Med. Hum. Genet."},{"key":"ref_91","first-page":"133","article-title":"Molecular analysis of SMN1 and NAIP genes in Egyptian patients with spinal muscular atrophy","volume":"108","author":"Essawi","year":"2007","journal-title":"Bratislavske lekarske listy"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1093\/hmg\/ddn357","article-title":"Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition","volume":"18","author":"Hauke","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1631\/jzus.B1500072","article-title":"Association between SMN2 methylation and disease severity in Chinese children with spinal muscular atrophy","volume":"17","author":"Cao","year":"2016","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/ejhg.2012.293","article-title":"Genome-wide analysis shows association of epigenetic changes in regulators of Rab and Rho GTPases with spinal muscular atrophy severity","volume":"21","author":"Zheleznyakova","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"0121964","DOI":"10.1371\/journal.pone.0121964","article-title":"Methylation levels of SLC23A2 and NCOR2 genes correlate with spinal muscular atrophy severity","volume":"10","author":"Zheleznyakova","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1152\/japplphysiol.00068.2010","article-title":"Epigenetics and environment: A complex relationship","volume":"109","author":"Aguilera","year":"2010","journal-title":"J. Appl. Physiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"9808","DOI":"10.1073\/pnas.171105098","article-title":"Treatment of spinal muscular atrophy by sodium butyrate","volume":"98","author":"Chang","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1093\/hmg\/ddg256","article-title":"Valproic acid increases the SMN2 protein level: A well-known drug as a potential therapy for spinal muscular atrophy","volume":"12","author":"Brichta","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_99","first-page":"647","article-title":"Valproic acid increases SMN levels in spinal muscular atrophy patient cells","volume":"54","author":"Sumner","year":"2003","journal-title":"Ann.Neurol. Offi. J. Am. Neurol. Assoc. Child Neurol. Soc."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.1471-4159.2006.03868.x","article-title":"In vitro and ex vivo evaluation of second-generation histone deacetylase inhibitors for the treatment of spinal muscular atrophy","volume":"98","author":"Hahnen","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/jhg.2016.61","article-title":"Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients","volume":"61","author":"Mohseni","year":"2016","journal-title":"J. Hum. Genet."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s00439-006-0186-1","article-title":"The benzamide M344, a novel histone deacetylase inhibitor, significantly increases SMN2 RNA\/protein levels in spinal muscular atrophy cells","volume":"120","author":"Riessland","year":"2006","journal-title":"Hum. Genet."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1172\/JCI29562","article-title":"Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy","volume":"117","author":"Avila","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.1093\/hmg\/ddp313","article-title":"LBH589 induces up to 10-fold SMN protein levels by several independent mechanisms and is effective even in cells from SMA patients non-responsive to valproate","volume":"18","author":"Garbes","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1111\/jnc.14935","article-title":"Combined treatment with the histone deacetylase inhibitor LBH589 and a splice-switch antisense oligonucleotide enhances SMN2 splicing and SMN expression in Spinal Muscular Atrophy cells","volume":"153","author":"Pagliarini","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e5268","DOI":"10.1371\/journal.pone.0005268","article-title":"Phase II open label study of valproic acid in spinal muscular atrophy","volume":"4","author":"Swoboda","year":"2009","journal-title":"PLoS ONE"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e12140","DOI":"10.1371\/journal.pone.0012140","article-title":"SMA CARNI-VAL trial part I: Double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy","volume":"5","author":"Swoboda","year":"2010","journal-title":"PLoS ONE"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/mus.25776","article-title":"Clinical trial of L-Carnitine and valproic acid in spinal muscular atrophy type I","volume":"57","author":"Krosschell","year":"2018","journal-title":"Muscle Nerve"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e21296","DOI":"10.1371\/journal.pone.0021296","article-title":"SMA carni-VAL trial part II: A prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy","volume":"6","author":"Kissel","year":"2011","journal-title":"PLoS ONE"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/mus.23904","article-title":"SMA valiant trial: A prospective, double-blind, placebo-controlled trial of valproic acid in ambulatory adults with spinal muscular atrophy","volume":"49","author":"Kissel","year":"2014","journal-title":"Muscle Nerve"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Darbar, I.A., Plaggert, P.G., Resende, M.B.D., Zanoteli, E., and Reed, U.C. (2011). Evaluation of muscle strength and motor abilities in children with type II and III spinal muscle atrophy treated with valproic acid. BMC Neurol., 11.","DOI":"10.1186\/1471-2377-11-36"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s40263-019-00606-6","article-title":"Efficacy and safety of valproic acid for spinal muscular atrophy: A systematic review and meta-analysis","volume":"33","author":"Elshafay","year":"2019","journal-title":"CNS Drugs"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/sj.ejhg.5201320","article-title":"Phenylbutyrate increases SMN gene expression in spinal muscular atrophy patients","volume":"13","author":"Brahe","year":"2005","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.nmd.2003.11.006","article-title":"Pilot trial of phenylbutyrate in spinal muscular atrophy","volume":"14","author":"Mercuri","year":"2004","journal-title":"Neuromuscul. Disord."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1212\/01.wnl.0000249142.82285.d6","article-title":"Randomized, double-blind, placebo-controlled trial of phenylbutyrate in spinal muscular atrophy","volume":"68","author":"Mercuri","year":"2007","journal-title":"Neurology"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3555","DOI":"10.1002\/j.1460-2075.1996.tb00725.x","article-title":"A novel nuclear structure containing the survival of motor neurons protein","volume":"15","author":"Liu","year":"1996","journal-title":"EMBO J."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.semcdb.2014.04.026","article-title":"SMN control of RNP assembly: From post-transcriptional gene regulation to motor neuron disease","volume":"32","author":"Li","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1177\/1073858417705059","article-title":"The actin cytoskeleton in SMA and ALS: How does it contribute to motoneuron degeneration?","volume":"24","author":"Hensel","year":"2018","journal-title":"Neuroscientist"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.conb.2016.04.004","article-title":"A role for the survival of motor neuron protein in mRNP assembly and transport","volume":"39","author":"Bassell","year":"2016","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.molmed.2015.08.003","article-title":"UBA1: At the crossroads of ubiquitin homeostasis and neurodegeneration","volume":"21","author":"Groen","year":"2015","journal-title":"Trends Mol. Med."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Boyd, P.J., Tu, W.Y., Shorrock, H.K., Groen, E.J., Carter, R.N., Powis, R.A., Thomson, S.R., Thomson, D., Graham, L.C., and Motyl, A.A. (2017). Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006744"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1523\/JNEUROSCI.4434-08.2009","article-title":"Impaired synaptic vesicle release and immaturity of neuromuscular junctions in spinal muscular atrophy mice","volume":"29","author":"Kong","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"10337","DOI":"10.1073\/pnas.1104928108","article-title":"Interaction of survival of motor neuron (SMN) and HuD proteins with mRNA cpg15 rescues motor neuron axonal deficits","volume":"108","author":"Akten","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"3914","DOI":"10.1523\/JNEUROSCI.3631-10.2011","article-title":"The survival of motor neuron (SMN) protein interacts with the mRNA-binding protein HuD and regulates localization of poly (A) mRNA in primary motor neuron axons","volume":"31","author":"Fallini","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_125","first-page":"10983","article-title":"High-affinity RNA targets of the Survival Motor Neuron protein reveal diverse preferences for sequence and structural motifs","volume":"46","author":"Ottesen","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.molmed.2012.11.002","article-title":"Spinal muscular atrophy: Going beyond the motor neuron","volume":"19","author":"Hamilton","year":"2013","journal-title":"Trends Mol. Med."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Besse, A., Astord, S., Marais, T., Roda, M., Giroux, B., Lejeune, F.X., Relaix, F., Smeriglio, P., Barkats, M., and Biferi, M.G. (2020). AAV9-mediated expression of SMN restricted to neurons does not rescue the spinal muscular atrophy phenotype in mice. Mol. Ther.","DOI":"10.1016\/j.ymthe.2020.05.011"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"4817","DOI":"10.1172\/JCI124120","article-title":"Age-dependent SMN expression in disease-relevant tissue and implications for SMA treatment","volume":"129","author":"Ramos","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Wadman, R.I., Stam, M., Jansen, M.D., van der Weegen, Y., Wijngaarde, C.A., Harschnitz, O., Sodaar, P., Braun, K.P., Dooijes, D., and Lemmink, H.H. (2016). A comparative study of SMN protein and mRNA in blood and fibroblasts in patients with spinal muscular atrophy and healthy controls. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0167087"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41582-018-0058-z","article-title":"Neurofilaments as biomarkers in neurological disorders","volume":"14","author":"Khalil","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jns.2005.03.015","article-title":"Neurofilament phosphoforms: Surrogate markers for axonal injury, degeneration and loss","volume":"233","author":"Petzold","year":"2005","journal-title":"J. Neurol. Sci."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"a018309","DOI":"10.1101\/cshperspect.a018309","article-title":"Neurofilaments and neurofilament proteins in health and disease","volume":"9","author":"Yuan","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0165-5728(87)90049-X","article-title":"Phosphorylation protects neurofilaments against proteolysis","volume":"14","author":"Goldstein","year":"1987","journal-title":"J. Neuroimmunol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1002\/acn3.779","article-title":"Neurofilament as a potential biomarker for spinal muscular atrophy","volume":"6","author":"Darras","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s00415-019-09547-y","article-title":"Neurofilament light chain in serum of adolescent and adult SMA patients under treatment with nusinersen","volume":"267","author":"Wurster","year":"2020","journal-title":"J. Neurol."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Totzeck, A., Stolte, B., Kizina, K., Bolz, S., Schlag, M., Thimm, A., Kleinschnitz, C., and Hagenacker, T. (2019). Neurofilament heavy chain and tau protein are not elevated in cerebrospinal fluid of adult patients with spinal muscular atrophy during loading with nusinersen. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215397"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nrneurol.2010.4","article-title":"Cerebrospinal fluid and plasma biomarkers in Alzheimer disease","volume":"6","author":"Blennow","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S1474-4422(16)00070-3","article-title":"CSF and blood biomarkers for the diagnosis of Alzheimer\u2019s disease: A systematic review and meta-analysis","volume":"15","author":"Olsson","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1007\/s00415-018-9008-3","article-title":"Diagnostic and prognostic power of CSF Tau in amyotrophic lateral sclerosis","volume":"265","author":"Scarafino","year":"2018","journal-title":"J. Neurol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1136\/jnnp-2018-320033","article-title":"Neurofilaments and tau in CSF in an infant with SMA type 1 treated with nusinersen","volume":"90","author":"Winter","year":"2019","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1172\/JCI131989","article-title":"Muscle-specific SMN reduction reveals motor neuron\u2014Independent disease in spinal muscular atrophy models","volume":"130","author":"Kim","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"e93329","DOI":"10.1371\/journal.pone.0093329","article-title":"Skeletal muscle DNA damage precedes spinal motor neuron DNA damage in a mouse model of Spinal Muscular Atrophy (SMA)","volume":"9","author":"Fayzullina","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"e921","DOI":"10.1212\/WNL.0000000000008762","article-title":"Serum creatinine is a biomarker of progressive denervation in spinal muscular atrophy","volume":"94","author":"Alves","year":"2020","journal-title":"Neurology"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"e35462","DOI":"10.1371\/journal.pone.0035462","article-title":"Candidate proteins, metabolites and transcripts in the Biomarkers for Spinal Muscular Atrophy (BforSMA) clinical study","volume":"7","author":"Finkel","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.stem.2015.08.003","article-title":"Genome-wide RNA-Seq of human motor neurons implicates selective ER stress activation in spinal muscular atrophy","volume":"17","author":"Ng","year":"2015","journal-title":"Cell Stem Cell"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1093\/brain\/awy330","article-title":"Key role of SMN\/SYNCRIP and RNA-Motif 7 in spinal muscular atrophy: RNA-Seq and motif analysis of human motor neurons","volume":"142","author":"Rizzo","year":"2019","journal-title":"Brain"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1007\/s00401-020-02133-x","article-title":"Synaptotagmin 13 is neuroprotective across motor neuron diseases","volume":"139","author":"Nizzardo","year":"2020","journal-title":"Acta Neuropathol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13073-019-0703-1","article-title":"Molecular profiling for precision cancer therapies","volume":"12","author":"Malone","year":"2020","journal-title":"Genome Med."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.cmi.2017.10.013","article-title":"Next-generation sequencing technologies and their application to the study and control of bacterial infections","volume":"24","author":"Besser","year":"2018","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"e02007-18","DOI":"10.1128\/mBio.02007-18","article-title":"BacCapSeq: A platform for diagnosis and characterization of bacterial infections","volume":"9","author":"Allicock","year":"2018","journal-title":"MBio"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.stem.2018.05.019","article-title":"Toward precision medicine for neurological and neuropsychiatric disorders","volume":"23","author":"Gibbs","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Seferian, A.M., Moraux, A., Canal, A., Decostre, V., Diebate, O., Le Moing, A.G., Gidaro, T., Deconinck, N., Van Parys, F., and Vereecke, W. (2015). Upper limb evaluation and one-year follow up of non-ambulant patients with spinal muscular atrophy: An observational multicenter trial. 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