Do Not Trust the Pedigree: Reduced and Sex‐Dependent Penetrance at a Novel Mutation Hotspot in ATL1 Blurs Autosomal Dominant Inheritance of Spastic Paraplegia. Issue 6 (5th April 2013)

• Record Type: Journal Article
• Authors: Varga, Rita‐Eva; Schüle, Rebecca; Fadel, Hicham; Valenzuela, Irene; Speziani, Fiorella; Gonzalez, Michael; Rudenskaia, Galina; Nürnberg, Gudrun; Thiele, Holger; Altmüller, Janine; Alvarez, Victoria; Gamez, Josep; Garbern, James Y.; Nürnberg, Peter; Zuchner, Stephan; Beetz, Christian
• Is Part Of: Human mutation. Volume 34:Issue 6(2013:Jun.)
• Page Start: 860
• Page End: 863
• Publication Date: 2013-04-05
• Subjects: Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.22309
• Languages: English
• ISSNs: 1059-7794

Abstract

<abstract abstract-type="graphical" xml:lang="en" id="humu22309-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Inheritance patterns usually guide gene selection in mutational screening strategies. By whole exome sequencing of index cases with apparently novel forms of spastic paraplegia, we identify a mutational hotspot in the known dominant gene ATL1 and show that corresponding alterations are associated with a highly reduced and partially sex‐dependent risk of developing the disease. Our findings suggest that misleading family history may contribute to missing heritability in genetically heterogeneous disorders. <boxed-text content-type="graphic" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgg20pg587n" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> </abstract>