{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:33:03Z","timestamp":1777660383472,"version":"3.51.4"},"reference-count":56,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T00:00:00Z","timestamp":1601510400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Genetic Testing and Molecular Biomarkers"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Spinal muscular atrophy (SMA) is traditionally molecularly diagnosed by multiplex ligation-dependent probe amplification or quantitative polymerase chain reaction (qPCR). SMA analyses are not routinely incorporated into gene panel analyses for individuals with suspected SMA or broader neuromuscular indications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim:<\/jats:title>\n                    <jats:p>We sought to determine whether a next-generation sequencing (NGS) approach that integrates SMA analyses into a multigene neuromuscular disorders panel could detect undiagnosed SMA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>\n                      Sequence and copy number variants of the\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">SMN2<\/jats:italic>\n                      genes were simultaneously analyzed in samples from 5304 unselected individuals referred for testing using an NGS-based 122-gene neuromuscular panel. This diagnostic approach was validated using DNA from 68 individuals who had been previously diagnosed with SMA via quantitative PCR for\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">SMN2<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Homozygous loss of\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      was detected in 47 unselected individuals. Heterozygous loss of\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      was detected in 118 individuals; 8 had an indeterminate variant in \u201c\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">SMN2<\/jats:italic>\n                      \u201d that supported an SMA diagnosis but required additional disambiguation. Of the remaining SMA carriers, 44 had pathogenic variants in other genes. Concordance rates between NGS and qPCR were 100% and 93% for\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">SMN2<\/jats:italic>\n                      copy numbers, respectively. Where there was disagreement, phenotypes were more consistent with the\n                      <jats:italic toggle=\"yes\">SMN2<\/jats:italic>\n                      results from NGS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Integrating NGS-based SMA testing into a multigene neuromuscular panel allows a single assay to diagnose SMA while comprehensively assessing the spectrum of variants that can occur in individuals with broad differential diagnoses or nonspecific\/overlapping neuromuscular features.<\/jats:p>\n                  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