{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:19:07Z","timestamp":1789165147650,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spastic Paraplegia Type 78 (SPG78) is a rare form of hereditary spastic paraplegia (HSP), mainly characterized by late\u2010onset lower\u2010limb spasticity, muscle weakness, and in some cases cerebellar dysfunction and cognitive impairment. Understanding its genetic background is essential to distinguish it from other autosomal recessive types of HSP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A pathogenic variant screening in a Spanish HSP patient was carried out by whole\u2010exome sequencing, followed by a software filtering process and validation of candidate variants by Sanger sequencing. The pathogenicity of the selected variants was evaluated by In Silico predictions and a segregation analysis including the proband and 16 family members.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Two variants in the\n                      <jats:italic>ATP13A2<\/jats:italic>\n                      gene, predicted to have damaging effects by In Silico analyses, were considered potentially pathogenic: NM022089.4:c.649G&gt;A (rs199961048), previously associated with SPG78 but with uncertain clinical significance, and NM_022089.4:c.2097delC, an unreported variant. The segregation analysis revealed that both variants were present in compound heterozygosity in the proband and two affected siblings, while unaffected relatives carried only one or none of the variants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that the two variants are pathogenic when occurring in compound heterozygosity and, therefore, should be included in the genetic spectrum of SPG78 diagnosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70073","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T02:23:43Z","timestamp":1739327023000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spastic Paraplegia Type 78 Associated With\n                    <i>ATP13A2<\/i>\n                    Gene Variants in Compound Heterozygosity"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2888-7595","authenticated-orcid":false,"given":"R. Bermejo","family":"Ram\u00edrez","sequence":"first","affiliation":[{"name":"Progenie Molecular S.L.U.  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2798-9970","authenticated-orcid":false,"given":"N. Villena","family":"Gasc\u00f3","sequence":"additional","affiliation":[{"name":"Progenie Molecular S.L.U.  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0159-9457","authenticated-orcid":false,"given":"L. Ruiz","family":"Palmero","sequence":"additional","affiliation":[{"name":"Progenie Molecular S.L.U.  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9081-9332","authenticated-orcid":false,"given":"G. A. Ribes","family":"Bueno","sequence":"additional","affiliation":[{"name":"Progenie Molecular S.L.U.  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8264-6512","authenticated-orcid":false,"given":"E. Seiti","family":"Yamanaka","sequence":"additional","affiliation":[{"name":"Progenie Molecular S.L.U.  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9559-2201","authenticated-orcid":false,"given":"J. D. Arroyo","family":"And\u00fajar","sequence":"additional","affiliation":[{"name":"Progenie Molecular S.L.U.  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