{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:17:14Z","timestamp":1787019434158,"version":"build-2736575974"},"reference-count":28,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100008762","name":"Genome Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010787","name":"Genome Alberta","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012171","name":"Ontario Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012171","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Genome Quebec"},{"DOI":"10.13039\/501100000092","name":"Ontario Genomics Institute","doi-asserted-by":"publisher","award":["OGI-147"],"award-info":[{"award-number":["OGI-147"]}],"id":[{"id":"10.13039\/501100000092","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000233","name":"Genome British Columbia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000233","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014429","name":"Children's Hospital of Eastern Ontario Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014429","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neuromuscular Diseases"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hereditary spastic paraplegia (HSP) is a heterogenous group of rare genetic disorders characterized by progressive corticospinal and dorsal spinal cord axonal degeneration manifesting as muscle weakness and spasticity of the lower extremities. Over 98% of solved HSP cases are caused by pathogenic variants in the nuclear DNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case<\/jats:title>\n                    <jats:p>\n                      We report a family carrying the m.9035T\u2009&gt;\u2009C [p.(Leu170Pro)] pathogenic variant in the mitochondrial\n                      <jats:italic toggle=\"yes\">MT<\/jats:italic>\n                      -\n                      <jats:italic toggle=\"yes\">ATP6<\/jats:italic>\n                      gene in the setting of maternally inherited, late-onset HSP. The proband (age 67 years) presented with classical, late-onset, pure HSP. Her affected daughter (age 39 years) developed late-onset, complex HSP, with asymmetrical axonal sensorimotor polyneuropathy. Her second daughter (age 46 years) carried the same pathogenic variant with high heteroplasmy but was clinically unaffected at last assessment, suggesting age-dependent or incomplete penetrance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary of literature<\/jats:title>\n                    <jats:p>The substitution of a leucine for a proline affects a highly conserved transmembrane helix of the subunit \u201ca\u201d at a key functional domain in the mitochondrial ATP synthase complex. The m.9035T\u2009&gt;\u2009C variant has been reported in several families presenting with common phenotypic presentations of ATP6-related disorders such as maternally inherited Leigh syndrome (MILS) and the syndrome of neuropathy, ataxia, and retinitis pigmentosa (NARP). HSP is a rare presentation in ATP6-related disorders; mitochondrial ATP6-induced HSP has previously been published in only one family carrying a homoplasmic m.9176T\u2009&gt;\u2009C [p.(Leu217Pro)] variant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This report highlights the role of\n                      <jats:italic toggle=\"yes\">MT-ATP6<\/jats:italic>\n                      pathogenic variants in complex and pure HSP and raises the relevance of genetic testing of\n                      <jats:italic toggle=\"yes\">MT-ATP6<\/jats:italic>\n                      in undiagnosed cases of sporadic or maternally inherited HSP.\n                    <\/jats:p>\n                  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