caa a22 4500 445364440 CHVBK 20180317142925.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s10048-010-0269-y doi (NATIONALLICENCE)springer-10.1007/s10048-010-0269-y Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms [Elektronische Daten] [Jens Schuster, Jimmy Sundblom, Ann-Charlotte Thuresson, Sharon Hassin-Baer, Thomas Klopstock, Martin Dichgans, Oren Cohen, Raili Raininko, Atle Melberg, Niklas Dahl] Adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms features micturition urgency, constipation, erectile dysfunction, and orthostatic hypotension, usually followed by pyramidal signs and ataxia. Peripheral nerve conduction is normal. The disease is often mistaken for multiple sclerosis in the initial phase. There is a characteristic pattern of white matter changes in the brain and spinal cord on magnetic resonance imaging (MRI), mild atrophy of the brain, and a more marked atrophy of the spinal cord. ADLD is associated with duplications of the lamin B1 (LMNB1) gene but the mechanism by which the rearrangement conveys the phenotype is not fully defined. We analyzed four unrelated families segregating ADLD with autonomic symptoms for duplications of the LMNB1 gene. A single nucleotide polymorphism (SNP) array analysis revealed novel duplications spanning the entire LMNB1 gene in probands from each of the four families. We then analyzed the expression of lamin B1 in peripheral leukocytes by Western blot analysis in five patients from two available families. The protein levels of lamin B1 were found significantly increased. These results indicate that the ADLD phenotype associated with LMNB1 duplications is mediated by increased levels of the lamin B1 protein. Furthermore, we show that a molecular diagnosis for ADLD with autonomic symptoms can be obtained by a direct analysis of lamin B1 in peripheral leukocytes. Springer-Verlag, 2011 LMNB1 nationallicence Duplication nationallicence Autosomal dominant leukodystrophy (ADLD) nationallicence Autonomic symptoms nationallicence Lamin B1 nationallicence ADLD : Autosomal dominant leukodystrophy nationallicence CNV : Copy number variation nationallicence MR : Magnetic resonance nationallicence SNP : Single nucleotide polymorphism nationallicence PCR : Polymerase chain reaction nationallicence Schuster Jens Department of Genetics and Pathology, The Rudbeck Laboratory and Science for Life Laboratory, Uppsala University and University Hospital, SE-751 85, Uppsala, Sweden aut Sundblom Jimmy Department of Neuroscience, Neurology, Uppsala University and University Hospital, Uppsala, Sweden aut Thuresson Ann-Charlotte Department of Genetics and Pathology, The Rudbeck Laboratory and Science for Life Laboratory, Uppsala University and University Hospital, SE-751 85, Uppsala, Sweden aut Hassin-Baer Sharon Department of Neurology and Parkinson's Disease and Movement Disorders Clinic, Sagol Neuroscience Center, Chaim Sheba Medical Center, Tel Hashomer, Israel aut Klopstock Thomas Friedrich Baur Institute, Department of Neurology, Ludwig Maximilians University, Ziemssenstr. 1a, Munich, Germany aut Dichgans Martin Department of Neurology, Neurologische Klinik, Klinikum Grosshadern, Ludwig Maximilians University, Marchioninistr. 15, Munich, Germany aut Cohen Oren Department of Neurology and Parkinson's Disease and Movement Disorders Clinic, Sagol Neuroscience Center, Chaim Sheba Medical Center, Tel Hashomer, Israel aut Raininko Raili Department of Radiology, Uppsala University and University Hospital, Uppsala, Sweden aut Melberg Atle Department of Neuroscience, Neurology, Uppsala University and University Hospital, Uppsala, Sweden aut Dahl Niklas Department of Genetics and Pathology, The Rudbeck Laboratory and Science for Life Laboratory, Uppsala University and University Hospital, SE-751 85, Uppsala, Sweden aut neurogenetics Springer-Verlag 12/1(2011-02-01), 65-72 1364-6745 12:1<65 2011 12 10048 https://doi.org/10.1007/s10048-010-0269-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10048-010-0269-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Schuster Jens Department of Genetics and Pathology, The Rudbeck Laboratory and Science for Life Laboratory, Uppsala University and University Hospital, SE-751 85, Uppsala, Sweden aut NATIONALLICENCE 700 1- Sundblom Jimmy Department of Neuroscience, Neurology, Uppsala University and University Hospital, Uppsala, Sweden aut NATIONALLICENCE 700 1- Thuresson Ann-Charlotte Department of Genetics and Pathology, The Rudbeck Laboratory and Science for Life Laboratory, Uppsala University and University Hospital, SE-751 85, Uppsala, Sweden aut NATIONALLICENCE 700 1- Hassin-Baer Sharon Department of Neurology and Parkinson's Disease and Movement Disorders Clinic, Sagol Neuroscience Center, Chaim Sheba Medical Center, Tel Hashomer, Israel aut NATIONALLICENCE 700 1- Klopstock Thomas Friedrich Baur Institute, Department of Neurology, Ludwig Maximilians University, Ziemssenstr. 1a, Munich, Germany aut NATIONALLICENCE 700 1- Dichgans Martin Department of Neurology, Neurologische Klinik, Klinikum Grosshadern, Ludwig Maximilians University, Marchioninistr. 15, Munich, Germany aut NATIONALLICENCE 700 1- Cohen Oren Department of Neurology and Parkinson's Disease and Movement Disorders Clinic, Sagol Neuroscience Center, Chaim Sheba Medical Center, Tel Hashomer, Israel aut NATIONALLICENCE 700 1- Raininko Raili Department of Radiology, Uppsala University and University Hospital, Uppsala, Sweden aut NATIONALLICENCE 700 1- Melberg Atle Department of Neuroscience, Neurology, Uppsala University and University Hospital, Uppsala, Sweden aut NATIONALLICENCE 700 1- Dahl Niklas Department of Genetics and Pathology, The Rudbeck Laboratory and Science for Life Laboratory, Uppsala University and University Hospital, SE-751 85, Uppsala, Sweden aut NATIONALLICENCE 773 0- neurogenetics Springer-Verlag 12/1(2011-02-01), 65-72 1364-6745 12:1<65 2011 12 10048 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer