{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:49:46Z","timestamp":1786978186615,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T00:00:00Z","timestamp":1719446400000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Spastic paraplegia 11 (SPG11) is the most prevalent form of autosomal recessive hereditary spastic paraplegia, resulting from biallelic pathogenic variants in the\n                      <jats:italic>SPG11<\/jats:italic>\n                      gene (MIM *610844).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The proband is a 36\u2010year\u2010old female referred for genetic evaluation due to cognitive dysfunction, gait impairment, and corpus callosum atrophy (brain MRI was normal at 25\u2010years\u2010old). Diagnostic approaches included CGH array, next\u2010generation sequencing, and whole transcriptome sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CGH array revealed a 180 kb deletion located upstream of\n                      <jats:italic>SPG11<\/jats:italic>\n                      . Sequencing of\n                      <jats:italic>SPG11<\/jats:italic>\n                      uncovered two rare single nucleotide variants: the novel variant c.3143C&gt;T in exon 17 (in cis with the deletion), and the previously reported pathogenic variant c.6409C&gt;T in exon 34 (in trans). Whole transcriptome sequencing revealed that the variant c.3143C&gt;T caused exon 17 skipping.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We report a novel sequence variant in the\n                      <jats:italic>SPG11<\/jats:italic>\n                      gene resulting in exon 17 skipping, which, along with a nonsense variant, causes Spastic Paraplegia 11 in our proband. In addition, a deletion upstream of\n                      <jats:italic>SPG11<\/jats:italic>\n                      was identified in the patient, whose implication in the phenotype remains uncertain. Nonetheless, the deletion apparently affects cis\u2010regulatory elements of the gene, suggesting a potential new pathogenic mechanism underlying the disease in a subset of undiagnosed patients. Our findings further support the hypothesis that the origin of thin corpus callosum in patients with SPG11 is of progressive nature.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.2475","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T02:34:17Z","timestamp":1719542057000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unexpected complexity in the molecular diagnosis of spastic paraplegia 11"],"prefix":"10.1002","volume":"12","author":[{"given":"Irene","family":"Mademont\u2010Soler","sequence":"first","affiliation":[{"name":"\u00c0rea de Gen\u00e8tica Cl\u00ednica i Consell Gen\u00e8tic, Laboratori Cl\u00ednic Territorial Girona Institut Catal\u00e0 de la Salut  Girona Spain"},{"name":"Grup de Trastorns del Neurodesenvolupament Institut Investigaci\u00f3 Biom\u00e8dica de Girona  Girona 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