{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T08:17:35Z","timestamp":1789805855485,"version":"4.0.1"},"reference-count":39,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2010,7,28]],"date-time":"2010-07-28T00:00:00Z","timestamp":1280275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2010,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Seven autosomal recessive genes associated with juvenile and young\u2010onset Levodopa\u2010responsive parkinsonism have been identified. Mutations in <jats:italic>PRKN<\/jats:italic>, <jats:italic>DJ\u20101<\/jats:italic>, and <jats:italic>PINK1<\/jats:italic> are associated with a rather pure parkinsonian phenotype, and have a more benign course with sustained treatment response and absence of dementia. On the other hand, Kufor\u2010Rakeb syndrome has additional signs, which distinguish it clearly from Parkinson's disease including supranuclear vertical gaze palsy, myoclonic jerks, pyramidal signs, and cognitive impairment. Neurodegeneration with brain iron accumulation type I (Hallervorden\u2010Spatz syndrome) due to mutations in <jats:italic>PANK2<\/jats:italic> gene may share similar features with Kufor\u2010Rakeb syndrome. Mutations in three other genes, <jats:italic>PLA2G6<\/jats:italic> (PARK14), <jats:italic>FBXO7<\/jats:italic> (PARK15), and Spatacsin (SPG11) also produce clinical similar phenotypes in that they presented with rapidly progressive parkinsonism, initially responsive to Levodopa treatment but later, developed additional features including cognitive decline and loss of Levodopa responsiveness. Here, using homozygosity mapping and sequence analysis in families with complex parkinsonisms, we identified genetic defects in the <jats:italic>ATP13A2<\/jats:italic> (1 family), <jats:italic>PLA2G6<\/jats:italic> (1 family) <jats:italic>FBXO7<\/jats:italic> (2 families), and SPG11 (1 family). The genetic heterogeneity was surprising given their initially common clinical features. On careful review, we found the <jats:italic>FBXO7<\/jats:italic> cases to have a phenotype more similar to PRKN gene associated parkinsonism. The <jats:italic>ATP13A2<\/jats:italic> and <jats:italic>PLA2G6<\/jats:italic> cases were more seriously disabled with additional swallowing problems, dystonic features, severe in some, and usually pyramidal involvement including pyramidal weakness. These data suggest that these four genes account for many cases of Levodopa responsive parkinsonism with pyramidal signs cases formerly categorized clinically as pallido\u2010pyramidal syndrome. \u00a9 2010 Movement Disorder Society.<\/jats:p>","DOI":"10.1002\/mds.23221","type":"journal-article","created":{"date-parts":[[2010,7,28]],"date-time":"2010-07-28T21:54:13Z","timestamp":1280354053000},"page":"1791-1800","source":"Crossref","is-referenced-by-count":219,"title":["Early\u2010onset L\u2010dopa\u2010responsive parkinsonism with pyramidal signs due to <i>ATP13A2, PLA2G6, FBXO7<\/i> and <i>spatacsin<\/i> mutations"],"prefix":"10.1002","volume":"25","author":[{"given":"Coro","family":"Pais\u00e1n\u2010Ruiz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocio","family":"Guevara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Federoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasmet","family":"Hanagasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fardaz","family":"Sina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elahe","family":"Elahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne 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