{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T10:07:13Z","timestamp":1782986833013,"version":"3.54.5"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,11,30]],"date-time":"2009-11-30T00:00:00Z","timestamp":1259539200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>We sought to explore the genetic and molecular causes of Troyer syndrome, one of several complicated hereditary spastic paraplegias (HSPs). Troyer syndrome had been thought to be restricted to the Amish; however, we identified 2 Omani families with HSP, short stature, dysarthria and developmental delay\u2014core features of Troyer syndrome\u2014and a novel mutation in the <jats:italic>SPG20<\/jats:italic> gene, which is also mutated in the Amish. In addition, we analyzed <jats:italic>SPG20<\/jats:italic> expression throughout development to infer how disruption of this gene might generate the constellation of developmental and degenerative Troyer syndrome phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical characterization of 2 non\u2010Amish families with Troyer syndrome was followed by linkage and sequencing analysis. Quantitative polymerase chain reaction and in situ hybridization analysis of <jats:italic>SPG20<\/jats:italic> expression were carried out in embryonic and adult human and mouse tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two Omani families carrying a novel <jats:italic>SPG20<\/jats:italic> mutation displayed clinical features remarkably similar to the Amish patients with Troyer syndrome. <jats:italic>SPG20<\/jats:italic> mRNA is expressed broadly but at low relative levels in the adult brain; however, it is robustly and specifically expressed in the limbs, face, and brain during early morphogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Null mutations in <jats:italic>SPG20<\/jats:italic> cause Troyer syndrome, a specific clinical entity with developmental and degenerative features. Maximal expression of <jats:italic>SPG20<\/jats:italic> in the limb buds and forebrain during embryogenesis may explain the developmental origin of the skeletal and cognitive defects observed in this disorder. ANN NEUROL 2010;67:516\u2013525<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.21923","type":"journal-article","created":{"date-parts":[[2009,11,30]],"date-time":"2009-11-30T20:04:02Z","timestamp":1259611442000},"page":"516-525","source":"Crossref","is-referenced-by-count":32,"title":["Developmental and degenerative features in a complicated spastic paraplegia"],"prefix":"10.1002","volume":"67","author":[{"given":"M. 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