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About the Authors:
Thomas O. Crawford
* E-mail: [email protected]
Affiliation: Departments of Neurology and Pediatrics, The Johns Hopkins University, Baltimore, Maryland, United States of America
Sergey V. Paushkin
Affiliation: Spinal Muscular Atrophy Foundation, New York, New York, United States of America
Dione T. Kobayashi
Affiliation: Spinal Muscular Atrophy Foundation, New York, New York, United States of America
Suzanne J. Forrest
Affiliation: Spinal Muscular Atrophy Foundation, New York, New York, United States of America
Cynthia L. Joyce
Affiliation: Spinal Muscular Atrophy Foundation, New York, New York, United States of America
Richard S. Finkel
Affiliation: Departments of Neurology and Pediatrics, Children’s Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
Petra Kaufmann
Affiliation: Department of Neurology, Columbia University, New York, New York, United States of America
Kathryn J. Swoboda
Affiliation: Departments of Neurology and Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, United States of America
Danilo Tiziano
Affiliation: Instituto di Genetica Medica, Università Cattolica S. Cuore, Roma, Italy
Rosa Lomastro
Affiliation: Instituto di Genetica Medica, Università Cattolica S. Cuore, Roma, Italy
Rebecca H. Li
Affiliation: New England Research Institutes, Inc., Watertown, Massachusetts, United States of America
Felicia L. Trachtenberg
Affiliation: New England Research Institutes, Inc., Watertown, Massachusetts, United States of America
Thomas Plasterer
Affiliation: Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, United States of America
Karen S. Chen
Affiliation: Spinal Muscular Atrophy Foundation, New York, New York, United States of America
on behalf of the Pilot Study of Biomarkers for Spinal Muscular Atrophy (BforSMA) Trial Group
¶Members of the BforSMA Trial Group are listed inList S1.
Introduction
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder that manifests across a wide range of severity. The cardinal clinical feature of SMA – diffuse skeletal muscle weakness – is a consequence of dysfunction or loss of alpha motor neurons. SMA is caused by loss-of-function mutations or deletions of the gene SMN1 (Gene ID = 6606). A wide range of disease severity can be partially attributed to the presence of variable copy number of a neighboring near-identical gene, SMN2 (Gene ID = 6607) [1]–[3]. A single base pair difference between these two genes greatly reduces the efficiency of exon 7 inclusion into mature transcripts from the SMN2 gene, but...