title: Lamin B1 duplications cause autosomal dominant leukodystrophy.
abstract: 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.
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, California 94158, USA.
authors.forename: Quasar S
authors.initials: QS
authors.lastname: Padiath
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Saigoh
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.forename: Hideaki
authors.initials: H
authors.lastname: Asahara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamada
authors.forename: Anulf
authors.initials: A
authors.lastname: Koeppen
authors.forename: Kirk
authors.initials: K
authors.lastname: Hogan
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Ptácek
authors.forename: Ying-Hui
authors.initials: YH
authors.lastname: Fu
mesh_terms: D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000473:pathology / Q000502:physiology; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D004331:Drosophila melanogaster / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D005799:Genes, Dominant; D008040:Genetic Linkage; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics* / Q000473:pathology; D006801:Humans; D034921:Lamin Type B / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data
chemical_list: D034921:Lamin Type B