Nature Genetics
- 38, 1114 - 1123 (2006)
Published online: 3 September 2006; Corrected online: 12 September 2006 ; Corrected online: 22 January 2007 | doi:10.1038/ng1872
There is a Corrigendum (February 2007) associated with this Article.
Lamin B1 duplications cause autosomal dominant leukodystrophyQuasar S Padiath1, Kazumasa Saigoh1, 8, Raphael Schiffmann2, Hideaki Asahara3, Takeshi Yamada4, Anulf Koeppen5, Kirk Hogan6, Louis J Ptá ek1, 7 & Ying-Hui Fu11
Department of Neurology, University of California, San Francisco, San Francisco, California, USA 94158. 2
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, US National Institutes of Health, Bethesda, Maryland 20892, USA. 3
Department of Neurology, Faculty of Medicine, Kyushu University, Kyushu, Japan. 4
Department of Neurology, Iizuka Hospital, Iizuka City, Japan. 5
Veterans Administration Medical Center and Department of Neurology, Albany Medical College, Albany 12208, New York, USA. 6
Department of Anesthesiology, University of Wisconsin, Madison, Wisconsin 53792, USA. 7
Howard Hughes Medical Institute, San Francisco, California 94158, USA. 8
Present address: Department of Neurology, Kinki University School of Medicine, Osaka, Japan.
Correspondence should be addressed to Ying-Hui Fu yhf@neugenes.org NOTE: The construct we described as moody-GAL4 has a name that was assigned to a different construct in a previously published paper. In this paper, it should be referred to as SPG-GAL4 (for 'sub-perineural-glia-GAL4'). This construct was a gift from R. Bainton (University of California San Francisco School of Medicine). The construction and activity of this promoter will be published elsewhere (R. Bainton, personal communication). The error has been corrected in the PDF version of the article.Adult-onset autosomal dominant leukodystrophy (ADLD) is a slowly progressive neurological disorder characterized by symmetrical widespread myelin loss in the central nervous system, with a phenotype similar to chronic progressive multiple sclerosis. In this study, we identify a genomic duplication that causes ADLD. Affected individuals carry an extra copy of the gene for the nuclear laminar protein lamin B1, resulting in increased gene dosage in brain tissue from individuals with ADLD. Increased expression of lamin B1 in Drosophila melanogaster resulted in a degenerative phenotype. In addition, an abnormal nuclear morphology was apparent when cultured cells overexpressed this protein. This is the first human disease attributable to mutations in the gene encoding lamin B1. Antibodies to lamin B are found in individuals with autoimmune diseases, and it is also an antigen recognized by a monoclonal antibody raised against plaques from brains of individuals with multiple sclerosis. This raises the possibility that lamin B may be a link to the autoimmune attack that occurs in multiple sclerosis.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
