5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2

Katharina Vill^{1

2}, Moritz Tacke³, Anna König³, Matthias Baumann⁴, Manuela Baumgartner⁵, Meike Steinbach⁶, Guenther Bernert⁷, Astrid Blaschek³, Marcus Deschauer⁸, Marina Flotats-Bastardas⁹, Johannes Friese¹⁰, Susanne Goldbach¹¹, Martin Gross¹², René Günther¹³, Andreas Hahn¹⁴, Tim Hagenacker¹⁵, Erwin Hauser¹⁶, Veronka Horber¹⁷, Sabine Illsinger¹⁸, Jessika Johannsen¹⁹, Christoph Kamm²⁰, Jan C Koch²¹, Heike Koelbel²², Cornelia Koehler²³, Kirsten Kolzter²⁴, Hanns Lochmüller^{25

26}, Albert Ludolph^{27

28}, Alexander Mensch²⁹, Gerd Meyer Zu Hoerste³⁰, Monika Mueller³¹, Wolfgang Mueller-Felber³, Christoph Neuwirth³², Susanne Petri³³, Kristina Probst-Schendzielorz³⁴, Manuel Pühringer³⁵, Robert Steinbach³⁶, Ulrike Schara-Schmidt²², Mareike Schimmel³⁷, Bertold Schrank³⁸, Oliver Schwartz³⁹, Kurt Schlachter⁴⁰, Annette Schwerin-Nagel⁴¹, Gudrun Schreiber⁴², Martin Smitka⁴³, Raffi Topakian⁴⁴, Regina Trollmann⁴⁵, Matthias Tuerk^{46

47}, Manuela Theophil⁴⁸, Christian Rauscher⁴⁹, Mathias Vorgerd⁵⁰, Maggie C Walter⁵¹, Markus Weiler⁵², Claudia Weiss⁵³, Ekkehard Wilichowski⁵⁴, Claudia D Wurster²⁸, Gilbert Wunderlich^{55

56}, Daniel Zeller⁵⁷, Andreas Ziegler⁵⁸, Janbernd Kirschner^#²³, Astrid Pechmann^#²³; SMArtCARE study group

Affiliations

¹ Department of Pediatric Neurology and Developmental Medicine and LMU Center for Children With Medical Complexity, Dr. Von Hauner Children's Hospital, LMU Hospital, Ludwig-Maximilians-University, 80337, Munich, Germany. Katharina.vill@med.lmu.de.
² School of Medicine, Klinikum Rechts Der Isar, Department of Human Genetics, Technical University of Munich, Munich, Germany. Katharina.vill@med.lmu.de.
³ Department of Pediatric Neurology and Developmental Medicine and LMU Center for Children With Medical Complexity, Dr. Von Hauner Children's Hospital, LMU Hospital, Ludwig-Maximilians-University, 80337, Munich, Germany.
⁴ Division of Pediatric Neurology, Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria.
⁵ Department of Children and Adolescents, Ordensklinikum Linz Barmherzige Schwestern, Linz, Austria.
⁶ Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany.
⁷ Clinic for Pediatrics, Gesundheitsverbund Wien, Vienna, Austria.
⁸ School of Medicine, Klinikum Rechts Der Isar, Department of Neurology, Technical University of Munich, Munich, Germany.
⁹ Department of Neuropaediatrics, Saarland University Hospital, Homburg, Germany.
¹⁰ Department of Neuropediatrics, University Hospital Bonn, Center for Pediatrics, Bonn, Germany.
¹¹ Deutsche Gesellschaft Für Muskelkranke E.V., Freiburg, Germany.
¹² Department of Neurological Intensive Care and Rehabilitation, Evangelisches Krankenhaus Oldenburg, Oldenburg, Germany.
¹³ University Hospital Carl Gustav Carus Dresden at Technische Universität Dresden, Dresden, Germany.
¹⁴ Department of Child Neurology, Justus-Liebig-University Gießen, Gießen, Germany.
¹⁵ Department of Neurology, and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, Essen, Germany.
¹⁶ Department for Neuropädiatrie, Landeskrankenhaus Mödling, Mödling, Austria.
¹⁷ Department of Paediatric Neurology, University Children's Hospital Tübingen, Tübingen, Germany.
¹⁸ Hannover Medical School, Clinic for Pediatric Kidney-, Liver- and Metabolic Diseases, Hannover, Germany.
¹⁹ Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
²⁰ Department of Neurology, University of Rostock, Rostock, Germany.
²¹ Klinik Für Neurologie Universitätsmedizin Göttingen, Göttingen, Germany.
²² Department of Pediatric Neurology, Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, University Duisburg-Essen, Essen, Germany.
²³ Klinik Für Kinder-Und Jugendmedizin der Ruhr-Universität Bochum Im St. Josef-Hospital, Bochum, Germany.
²⁴ Kliniken Köln, Sozialpädiatrisches Zentrum, Cologne, Germany.
²⁵ Division of Neurology, Department of Medicine, Children's Hospital of Eastern Ontario Research Institute, The Ottawa Hospital and Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada.
²⁶ Department of Neuropediatrics and Muscle Disorders, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
²⁷ Department for Neurology, University of Ulm, Ulm, Germany.
²⁸ Department of Neurology, Ulm University, Ulm, Germany.
²⁹ Department of Neurology, University Medicine Halle, Halle, Saale, Germany.
³⁰ Department of Neurology, University Hospital Münster, Münster, Germany.
³¹ Department for Neuropediatrics, University of Wuerzburg, Würzburg, Germany.
³² Neuromuscular Diseases Unit/ALS Clinic, Kantonsspital St. Gallen, St. Gallen, Switzerland.
³³ Department of Neurology, Hannover Medical School, Hannover, Germany.
³⁴ Initiative SMA der Deutschen Gesellschaft Für Muskelkranke, Freiburg, Germany.
³⁵ Department of Pediatrics and Adolescent Medicine, Kepler University Hospital Linz, Linz, Austria.
³⁶ Department of Neurology, University Hospital Jena, Jena, Germany.
³⁷ Pediatric Neurology, Pediatrics and Adolescent Medicine, University Medical Center Augsburg, Augsburg, Germany.
³⁸ Department of Neurology, DKD Helios Klinik Wiesbaden, Wiesbaden, Germany.
³⁹ Universitätsklinikum Münster Klinik Für Kinder- Und Jugendpädiatrie- Neuropädiatrie, Albert-Schweitzer-Campus 1, Münster, Germany.
⁴⁰ Department of Neuropediatrics, Landeskrankenhaus Bregenz, Bregenz, Austria.
⁴¹ Medical University Graz Childrens Hospital, Graz, Austria.
⁴² Department of Neuropediatics, Klinikum Kassel, Kassel, Germany.
⁴³ Department of Neuropediatrics, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
⁴⁴ Department of Neurology, Academic Teaching Hospital Wels-Grieskirchen, Wels, Austria.
⁴⁵ Department of Pediatrics, Friedrich-Alexander Universität Erlangen-Nürnberg Pediatric Neurology, Erlangen, Germany.
⁴⁶ Department of Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
⁴⁷ Centre for Rare Diseases Erlangen (ZSEER), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg (FAU), Erlangen, Germany.
⁴⁸ DRK Kliniken Berlin - Westend Kinderklinik, Berlin, Germany.
⁴⁹ Department for Neuropediatrics, University of Salzburg, Salzburg, Austria.
⁵⁰ Department of Neurology, BG-University Hospital Bergmannsheil gGmbH, Heimer Institute for Muscle Research, Ruhr-University Bochum, Bochum, Germany.
⁵¹ Friedrich Baur Institute at the Department of Neurology, LMU University Hospital, Ludwig Maximilians University, Munich, Germany.
⁵² Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
⁵³ Charité - University Medicine Berlin, Center for Chronically Sick Children, Berlin, Germany.
⁵⁴ Department for Neuropediatrics, University Göttingen, Göttingen, Germany.
⁵⁵ German Center for Neurodegenerative Diseases, DZNE, Site Ulm, Ulm, Germany.
⁵⁶ Faculty of Medicine and University Hospital, Department of Neurology and Center for Rare Diseases, University of Cologne, Cologne, Germany.
⁵⁷ Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
⁵⁸ Center for Childhood and Adolescent Medicine, Department of Metabolic Medicine and Pediatric Neurology, University Hospital Heidelberg, Heidelberg, Germany.

^# Contributed equally.

PMID: 38409538
PMCID: PMC11055798
DOI: 10.1007/s00415-024-12188-5

5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2

Katharina Vill et al. J Neurol. 2024 May.

. 2024 May;271(5):2787-2797.

doi: 10.1007/s00415-024-12188-5. Epub 2024 Feb 27.

Authors

Affiliations

¹ Department of Pediatric Neurology and Developmental Medicine and LMU Center for Children With Medical Complexity, Dr. Von Hauner Children's Hospital, LMU Hospital, Ludwig-Maximilians-University, 80337, Munich, Germany. Katharina.vill@med.lmu.de.
² School of Medicine, Klinikum Rechts Der Isar, Department of Human Genetics, Technical University of Munich, Munich, Germany. Katharina.vill@med.lmu.de.
³ Department of Pediatric Neurology and Developmental Medicine and LMU Center for Children With Medical Complexity, Dr. Von Hauner Children's Hospital, LMU Hospital, Ludwig-Maximilians-University, 80337, Munich, Germany.
⁴ Division of Pediatric Neurology, Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria.
⁵ Department of Children and Adolescents, Ordensklinikum Linz Barmherzige Schwestern, Linz, Austria.
⁶ Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany.
⁷ Clinic for Pediatrics, Gesundheitsverbund Wien, Vienna, Austria.
⁸ School of Medicine, Klinikum Rechts Der Isar, Department of Neurology, Technical University of Munich, Munich, Germany.
⁹ Department of Neuropaediatrics, Saarland University Hospital, Homburg, Germany.
¹⁰ Department of Neuropediatrics, University Hospital Bonn, Center for Pediatrics, Bonn, Germany.
¹¹ Deutsche Gesellschaft Für Muskelkranke E.V., Freiburg, Germany.
¹² Department of Neurological Intensive Care and Rehabilitation, Evangelisches Krankenhaus Oldenburg, Oldenburg, Germany.
¹³ University Hospital Carl Gustav Carus Dresden at Technische Universität Dresden, Dresden, Germany.
¹⁴ Department of Child Neurology, Justus-Liebig-University Gießen, Gießen, Germany.
¹⁵ Department of Neurology, and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, Essen, Germany.
¹⁶ Department for Neuropädiatrie, Landeskrankenhaus Mödling, Mödling, Austria.
¹⁷ Department of Paediatric Neurology, University Children's Hospital Tübingen, Tübingen, Germany.
¹⁸ Hannover Medical School, Clinic for Pediatric Kidney-, Liver- and Metabolic Diseases, Hannover, Germany.
¹⁹ Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
²⁰ Department of Neurology, University of Rostock, Rostock, Germany.
²¹ Klinik Für Neurologie Universitätsmedizin Göttingen, Göttingen, Germany.
²² Department of Pediatric Neurology, Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, University Duisburg-Essen, Essen, Germany.
²³ Klinik Für Kinder-Und Jugendmedizin der Ruhr-Universität Bochum Im St. Josef-Hospital, Bochum, Germany.
²⁴ Kliniken Köln, Sozialpädiatrisches Zentrum, Cologne, Germany.
²⁵ Division of Neurology, Department of Medicine, Children's Hospital of Eastern Ontario Research Institute, The Ottawa Hospital and Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada.
²⁶ Department of Neuropediatrics and Muscle Disorders, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
²⁷ Department for Neurology, University of Ulm, Ulm, Germany.
²⁸ Department of Neurology, Ulm University, Ulm, Germany.
²⁹ Department of Neurology, University Medicine Halle, Halle, Saale, Germany.
³⁰ Department of Neurology, University Hospital Münster, Münster, Germany.
³¹ Department for Neuropediatrics, University of Wuerzburg, Würzburg, Germany.
³² Neuromuscular Diseases Unit/ALS Clinic, Kantonsspital St. Gallen, St. Gallen, Switzerland.
³³ Department of Neurology, Hannover Medical School, Hannover, Germany.
³⁴ Initiative SMA der Deutschen Gesellschaft Für Muskelkranke, Freiburg, Germany.
³⁵ Department of Pediatrics and Adolescent Medicine, Kepler University Hospital Linz, Linz, Austria.
³⁶ Department of Neurology, University Hospital Jena, Jena, Germany.
³⁷ Pediatric Neurology, Pediatrics and Adolescent Medicine, University Medical Center Augsburg, Augsburg, Germany.
³⁸ Department of Neurology, DKD Helios Klinik Wiesbaden, Wiesbaden, Germany.
³⁹ Universitätsklinikum Münster Klinik Für Kinder- Und Jugendpädiatrie- Neuropädiatrie, Albert-Schweitzer-Campus 1, Münster, Germany.
⁴⁰ Department of Neuropediatrics, Landeskrankenhaus Bregenz, Bregenz, Austria.
⁴¹ Medical University Graz Childrens Hospital, Graz, Austria.
⁴² Department of Neuropediatics, Klinikum Kassel, Kassel, Germany.
⁴³ Department of Neuropediatrics, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
⁴⁴ Department of Neurology, Academic Teaching Hospital Wels-Grieskirchen, Wels, Austria.
⁴⁵ Department of Pediatrics, Friedrich-Alexander Universität Erlangen-Nürnberg Pediatric Neurology, Erlangen, Germany.
⁴⁶ Department of Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
⁴⁷ Centre for Rare Diseases Erlangen (ZSEER), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg (FAU), Erlangen, Germany.
⁴⁸ DRK Kliniken Berlin - Westend Kinderklinik, Berlin, Germany.
⁴⁹ Department for Neuropediatrics, University of Salzburg, Salzburg, Austria.
⁵⁰ Department of Neurology, BG-University Hospital Bergmannsheil gGmbH, Heimer Institute for Muscle Research, Ruhr-University Bochum, Bochum, Germany.
⁵¹ Friedrich Baur Institute at the Department of Neurology, LMU University Hospital, Ludwig Maximilians University, Munich, Germany.
⁵² Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
⁵³ Charité - University Medicine Berlin, Center for Chronically Sick Children, Berlin, Germany.
⁵⁴ Department for Neuropediatrics, University Göttingen, Göttingen, Germany.
⁵⁵ German Center for Neurodegenerative Diseases, DZNE, Site Ulm, Ulm, Germany.
⁵⁶ Faculty of Medicine and University Hospital, Department of Neurology and Center for Rare Diseases, University of Cologne, Cologne, Germany.
⁵⁷ Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
⁵⁸ Center for Childhood and Adolescent Medicine, Department of Metabolic Medicine and Pediatric Neurology, University Hospital Heidelberg, Heidelberg, Germany.

^# Contributed equally.

PMID: 38409538
PMCID: PMC11055798
DOI: 10.1007/s00415-024-12188-5

Abstract

Newborn screening for 5qSMA offers the potential for early, ideally pre-symptomatic, therapeutic intervention. However, limited data exist on the outcomes of individuals with 4 copies of SMN2, and there is no consensus within the SMA treatment community regarding early treatment initiation in this subgroup. To provide evidence-based insights into disease progression, we performed a retrospective analysis of 268 patients with 4 copies of SMN2 from the SMArtCARE registry in Germany, Austria and Switzerland. Inclusion criteria required comprehensive baseline data and diagnosis outside of newborn screening. Only data prior to initiation of disease-modifying treatment were included. The median age at disease onset was 3.0 years, with a mean of 6.4 years. Significantly, 55% of patients experienced symptoms before the age of 36 months. 3% never learned to sit unaided, a further 13% never gained the ability to walk independently and 33% of ambulatory patients lost this ability during the course of the disease. 43% developed scoliosis, 6.3% required non-invasive ventilation and 1.1% required tube feeding. In conclusion, our study, in line with previous observations, highlights the substantial phenotypic heterogeneity in SMA. Importantly, this study provides novel insights: the median age of disease onset in patients with 4 SMN2 copies typically occurs before school age, and in half of the patients even before the age of three years. These findings support a proactive approach, particularly early treatment initiation, in this subset of SMA patients diagnosed pre-symptomatically. However, it is important to recognize that the register will not include asymptomatic individuals.

Keywords: SMN2; Age of onset; Molecular therapies; Neonatal screening; Pre-symptomatic treatment; SMA; Spinal muscular atrophy.

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Conflict of interest statement

AB has received travel expenses and speaker fees from Roche, Novartis, Sanofi Genzyme, Biogen and Santhera. AH has received speaker fees and honoraria for advisor activities from Biogen, Roche, and Novartis Gene Therapies, and research grants from Novartis Gene Therapies. AL is a member of Advisory Boards of Roche Pharma AG, Biogen, Alector and Amylyx. He received compensation for talks from Biologix, the German Society of Neurology, Biogen, Springer Medicine, Amylyx and the company Streamed Up! GmbH. He is involved in trials which are sponsored by Amylyx, Ferrer International, Novartis Research and Development, Mitsubishi Tanabe, Apellis Pharmaceuticals, Alexion, Orion Pharma, the European Union, BMBF, Biogen and Orphazyme, Ionis Pharmaceuticals, QurAlis and Alector. AM has received advisory board honoraria from Hormosan and Sanofi, outside of the submitted work. AP received compensation for advisory boards, training activities and research grants from Novartis and Biogen. AR received honoraria as speaker from Amylyx Pharmaceuticals and as consultant in advisory boards from Biogen and Argenx. RS received honoraria as speaker from ITF Pharma. AZ received compensation for advisory boards and speaker fees from Biogen, Novartis and Roche. He received research compensation from Biogen. CDW has received honoraria from Biogen as an advisory board member and for lectures and as a consultant and advisory board member from Hoffmann‑La Roche. She also received travel expenses from Biogen. CK has received compensation for advisory boards and speaker honoraria from Biogen, Roche and Ipsen, and unrestricted travel grants from Merz and Ipsen, outside of the submitted work. CN has received personal fees from Biogen and Hoffmann–La Roche outside of the submitted work for advisory boards. CW has received honoraria for advisory boards and presentations and travel expenses from Biogen, Avexis/Novartis and Roche. DZ received compensation from Biogen for participation on advisory boards, from Novartis for consultancy work, and travel compensation from Angelini Pharma outside of the submitted work. GMzH received compensation for serving on scientific advisory boards (Alexion, Roche, LFB, Immunovant) and speaker honoraria (Alexion, LFB). He has received scientific project funding from Biogen and Merck. GW has received advisory board honoraria and speaker fees from Alnylam, Biogen, Hormosan, Pfizer and Sobi outside of the submitted work. HK is serving on a scientific advisory board for Avexis and received travel expenses and speaker honoraria from Biogen, Pfizer, Roche, and Sanofi-Aventis. JJ received compensation for advisory boards and funding for travel or speaker honoraria from Avexis/Novartis, Biogen, ITF, Roche, PTC, Pfizer and Sarepta Therapeutics. JK received compensation for research and/or educational and consultancy activities from Biogen, Avexis/Novartis, Roche and Scholar Rock. KV has received received honoraria as an advisory board member, travel expenses and speaker fees from Biogen, Santhera, Orchard, ITF and Novartis. MB received compensation for advisory boards and speakers honoraria from Novartis, Biogen and Roche. MCW received speaker fees and compensation for advisory boards and consultancy activities from Biogen, Avexis/Novartis, Roche. MD has received personal fees as speaker/consultant from Biogen and Roche. MFB has received consultant fees from Biogen, Novartis and Hoffmann-La Roche and Biogen. MG has received an advisory board honorarium from Hoffmann-La Roche and a speaker fee from Novartis outside of the submitted work. MS received compensation for advisory boards from Roche, Eisai and Takeda. MW received advisory board and consultant honoraria from Biogen and Hoffmann-La Roche, and speaker honoraria and travel support for conference attendance from Biogen, outside of the submitted work. OS has served as a member of a scientific advisory board for Avexis and received travel expenses and speaker fees from Biogen. RT received speaker fees and compensation for advisory boards from Biogen, Roche, and PTC. SI received compensation for advisory board and speakers honoraria from Novartis and Roche. SG received consulting fees and speaker fees from Novartis. SP has received speaker fees, non-financial support and research support from Biogen, Roche, AL-S Pharma, Amylyx, Cytokinetics, Ferrer, ITF-Pharma, Zambon, PTC and Sanofi and served on advisory boards of Amylyx, Biogen, Roche, Zambon and ITF Pharma and research grants from the German Neuromuscular Society (DGM) and Neurodegenerative Research outside of the submitted work. TH received compensation for advisory boards, speaker fees and research grants from Roche, Novartis and Biogen. US has served as a member of a scientific advisory board and data safety monitoring board for Biogen, Avexis and Novartis and received speaker fees from Biogen, Avexis, PTC and Sanofi-Aventis. VH received compensation for advisory boards from Avexis/Novartis and Biogen. WMF has served as a member of a scientific advisory board for Biogen, Avexis, PTC, Sarepta, Sanofi-Aventis, Roche and Cytokinetics and received travel expenses and speaker fees from Biogen, Avexis, Novartis, PTC, Roche, Sarepta and Sanofi-Aventis.

Figures

**Fig. 1**
Kaplan–Meier curve for age at disease onset: by the age of 18 years, approximately 95% of patients with four copies of *SMN2* was affected by the disease

**Fig. 2**
A Kaplan–Meier curve for loss of walking ability. By the age of 54, 32.5% of our cohort had lost their ability to walk without assistance. Note: For 20% of patients in this study cohort who lost independent ambulation, the exact age is unknown. Accordingly, 20% of the patients who were still able to walk were subtracted to create this curve. B Ambulation as a function of age for the entire cohort. Missing values were estimated from all known values

**Fig. 3**
Results of the motor function tests in Baseline. The wide variability of the disease independent of age is evident, with patients ranging from severely to mildly affected in all age groups up to 69 years. It can be assumed for both HFSME and RULM, that full scores are expected from the age of six onwards. Reference values for the 6MWT are shaded in a grey area on the chart

See this image and copyright information in PMC

References

1. Burghes AH, Beattie CE. Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick? Nat Rev Neurosci. 2009;10(8):597–609. doi: 10.1038/nrn2670. - DOI - PMC - PubMed
1. Pellizzoni L, Yong J, Dreyfuss G. Essential role for the SMN complex in the specificity of snRNP assembly. Science. 2002;298(5599):1775–1779. doi: 10.1126/science.1074962. - DOI - PubMed
1. Verhaart IEC, et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy - a literature review. Orphanet J Rare Dis. 2017;12(1):124. doi: 10.1186/s13023-017-0671-8. - DOI - PMC - PubMed
1. Lefebvre S, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80(1):155–165. doi: 10.1016/0092-8674(95)90460-3. - DOI - PubMed
1. Lorson CL, et al. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci U S A. 1999;96(11):6307–6311. doi: 10.1073/pnas.96.11.6307. - DOI - PMC - PubMed

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5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2

Affiliations

5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2

Authors

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Abstract

Conflict of interest statement

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