{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T20:02:08Z","timestamp":1783368128385,"version":"3.54.6"},"reference-count":27,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:00:00Z","timestamp":1688515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:00:00Z","timestamp":1688515200000},"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":["Journal of Neuromuscular Diseases"],"published-print":{"date-parts":[[2023,9,8]]},"abstract":"<jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      The importance of early diagnosis of 5q-Spinal muscular atrophy (5q-SMA) has heightened as early intervention can significantly improve clinical outcomes. In 96% of cases, 5q-SMA is caused by a homozygous deletion of\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      . Around 4 % of patients carry a\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      deletion and a single-nucleotide variant (SNV) on the other allele. Traditionally, diagnosis is based on multiplex ligation probe amplification (MLPA) to detect homozygous or heterozygous exon 7 deletions in\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      . Due to high homologies within the\n                      <jats:italic toggle=\"yes\">SMN1\/SMN2<\/jats:italic>\n                      locus, sequence analysis to identify SNVs of the\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      gene is unreliable by standard Sanger or short-read next-generation sequencing (srNGS) methods.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>The objective was to overcome the limitations in high-throughput srNGS with the aim of providing SMA patients with a fast and reliable diagnosis to enable their timely therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      A bioinformatics workflow to detect homozygous\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      deletions and\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      SNVs on srNGS analysis was applied to diagnostic whole exome and panel testing for suggested neuromuscular disorders (1684 patients) and to fetal samples in prenatal diagnostics (260 patients). SNVs were detected by aligning sequencing reads from\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">SMN2<\/jats:italic>\n                      to an\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      reference sequence. Homozygous\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      deletions were identified by filtering sequence reads for the ,, gene-determining variant\u201c (GDV).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      10 patients were diagnosed with 5q-SMA based on (i)\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      deletion and hemizygous SNV (2 patients), (ii) homozygous\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      deletion (6 patients), and (iii) compound heterozygous SNVs in\n                      <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                      (2 patients).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Applying our workflow in srNGS-based panel and whole exome sequencing (WES) is crucial in a clinical laboratory, as otherwise patients with an atypical clinical presentation initially not suspected to suffer from SMA remain undiagnosed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jnd-221668","type":"journal-article","created":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T10:53:45Z","timestamp":1688727225000},"page":"835-846","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Closing the Gap - Detection of 5q-Spinal Muscular Atrophy by Short-Read Next-Generation Sequencing and Unexpected Results in a Diagnostic Patient 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