{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T01:57:49Z","timestamp":1781229469156,"version":"3.54.1"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,4,26]],"date-time":"2020-04-26T00:00:00Z","timestamp":1587859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Spinal muscular atrophy (SMA) is an inherited neuromuscular disease affecting 1 in 8,000 newborns. The majority of patients carry bi\u2010allelic variants in the survival of motor neuron 1 gene (<jats:italic>SMN1<\/jats:italic>). <jats:italic>SMN1<\/jats:italic> is located in a duplicated region on chromosome 5q13 that contains <jats:italic>Alu<\/jats:italic> elements and is predisposed to genomic rearrangements. Due to the genomic complexity of the <jats:italic>SMN<\/jats:italic> region and genetic heterogeneity, approximately 50% of SMA patients remain without genetic diagnosis that is a prerequisite for genetic treatments. In this work we describe the diagnostic odyssey of one SMA patient in whom routine diagnostics identified only a maternal heterozygous <jats:italic>SMN1\u0394(7\u20138)<\/jats:italic> deletion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We characterized <jats:italic>SMN<\/jats:italic> transcripts, assessed SMN protein content in peripheral blood mononuclear cells (PBMC), estimated <jats:italic>SMN<\/jats:italic> genes dosage, and mapped genomic rearrangement in the <jats:italic>SMN<\/jats:italic> region.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified an <jats:italic>Alu<\/jats:italic>\u2010mediated deletion encompassing exons 2a\u20105 of <jats:italic>SMN1<\/jats:italic> on the paternal allele and a complete deletion of <jats:italic>SMN1<\/jats:italic> on the maternal allele as the cause of SMA in this patient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>Alu<\/jats:italic>\u2010mediated rearrangements in <jats:italic>SMN1<\/jats:italic> can escape routine diagnostic testing. Parallel analysis of <jats:italic>SMN<\/jats:italic> gene dosage, <jats:italic>SMN<\/jats:italic> transcripts, and total SMN protein levels in PBMC can identify genomic rearrangements and should be considered in genetically undefined SMA cases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1238","type":"journal-article","created":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T02:59:33Z","timestamp":1587956373000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Spinal muscular atrophy caused by a novel <i>Alu<\/i>\u2010mediated deletion of exons 2a\u20105 in <i>SMN1<\/i> undetectable with routine genetic testing"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3362-0834","authenticated-orcid":false,"given":"Ivana","family":"Jedli\u010dkov\u00e1","sequence":"first","affiliation":[{"name":"Research Unit for Rare Diseases Department of Pediatrics and Adolescent Medicine First Faculty of Medicine Charles University Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0047-9405","authenticated-orcid":false,"given":"Anna","family":"P\u0159istoupilov\u00e1","sequence":"additional","affiliation":[{"name":"Research Unit for Rare Diseases Department of Pediatrics and Adolescent Medicine First Faculty of Medicine Charles University Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7011-4327","authenticated-orcid":false,"given":"Lenka","family":"Noskov\u00e1","sequence":"additional","affiliation":[{"name":"Research Unit for Rare Diseases Department of Pediatrics and Adolescent Medicine First Faculty of Medicine Charles University Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3549-6312","authenticated-orcid":false,"given":"Filip","family":"Majer","sequence":"additional","affiliation":[{"name":"Research Unit for Rare Diseases Department of Pediatrics and Adolescent Medicine First Faculty of Medicine Charles University Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2599-6479","authenticated-orcid":false,"given":"Viktor","family":"Str\u00e1neck\u00fd","sequence":"additional","affiliation":[{"name":"Research Unit for Rare Diseases Department of Pediatrics and Adolescent Medicine First Faculty of Medicine Charles University Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7787-832X","authenticated-orcid":false,"given":"Hana","family":"Hartmannov\u00e1","sequence":"additional","affiliation":[{"name":"Research Unit for Rare Diseases Department of Pediatrics and Adolescent Medicine First Faculty of Medicine Charles University Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9172-9945","authenticated-orcid":false,"given":"Kate\u0159ina","family":"Hoda\u0148ov\u00e1","sequence":"additional","affiliation":[{"name":"Research Unit for Rare Diseases Department of Pediatrics and Adolescent Medicine First Faculty of Medicine Charles University Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0180-1179","authenticated-orcid":false,"given":"Helena","family":"Tre\u0161lov\u00e1","sequence":"additional","affiliation":[{"name":"Research Unit for Rare Diseases Department of Pediatrics and Adolescent Medicine First Faculty of Medicine Charles University Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"H\u00fdblov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Medirex A.S. 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