PMID- 21225301
OWN - NLM
STAT- MEDLINE
DCOM- 20110506
LR  - 20231213
IS  - 1364-6753 (Electronic)
IS  - 1364-6745 (Linking)
VI  - 12
IP  - 1
DP  - 2011 Feb
TI  - Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal 
      dominant leukodystrophy (ADLD) with autonomic symptoms.
PG  - 65-72
LID - 10.1007/s10048-010-0269-y [doi]
AB  - 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.
FAU - Schuster, Jens
AU  - Schuster J
AD  - Department of Genetics and Pathology, The Rudbeck Laboratory and Science for Life 
      Laboratory, Uppsala University and University Hospital, SE-751 85, Uppsala, 
      Sweden.
FAU - Sundblom, Jimmy
AU  - Sundblom J
FAU - Thuresson, Ann-Charlotte
AU  - Thuresson AC
FAU - Hassin-Baer, Sharon
AU  - Hassin-Baer S
FAU - Klopstock, Thomas
AU  - Klopstock T
FAU - Dichgans, Martin
AU  - Dichgans M
FAU - Cohen, Oren S
AU  - Cohen OS
FAU - Raininko, Raili
AU  - Raininko R
FAU - Melberg, Atle
AU  - Melberg A
FAU - Dahl, Niklas
AU  - Dahl N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110112
PL  - United States
TA  - Neurogenetics
JT  - Neurogenetics
JID - 9709714
RN  - 0 (Lamin Type B)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Adult
MH  - Autonomic Nervous System Diseases/blood/*genetics/pathology
MH  - Brain/pathology
MH  - Case-Control Studies
MH  - Chromosomes, Human, Pair 5/genetics
MH  - Female
MH  - *Gene Duplication
MH  - Gene Expression
MH  - Genes, Dominant
MH  - Hereditary Central Nervous System Demyelinating 
      Diseases/blood/*genetics/pathology
MH  - Humans
MH  - Lamin Type B/blood/*genetics
MH  - Leukocytes/metabolism
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Pedigree
MH  - Phenotype
MH  - Polymorphism, Single Nucleotide
MH  - RNA, Messenger/blood/genetics
EDAT- 2011/01/13 06:00
MHDA- 2011/05/07 06:00
CRDT- 2011/01/13 06:00
PHST- 2010/08/11 00:00 [received]
PHST- 2010/11/30 00:00 [accepted]
PHST- 2011/01/13 06:00 [entrez]
PHST- 2011/01/13 06:00 [pubmed]
PHST- 2011/05/07 06:00 [medline]
AID - 10.1007/s10048-010-0269-y [doi]
PST - ppublish
SO  - Neurogenetics. 2011 Feb;12(1):65-72. doi: 10.1007/s10048-010-0269-y. Epub 2011 
      Jan 12.