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@ARTICLE{Giorgio:136985,
author = {Giorgio, Elisa and Rolyan, Harshvardhan and Kropp, Laura
and Chakka, Anish Baswanth and Yatsenko, Svetlana and Di
Gregorio, Eleonora and Lacerenza, Daniela and Vaula,
Giovanna and Talarico, Flavia and Mandich, Paola and Toro,
Camilo and Pierre, Eleonore Eymard and Labauge, Pierre and
Capellari, Sabina and Cortelli, Pietro and Vairo, Filippo
Pinto and Miguel, Diego and Stubbolo, Danielle and Marques,
Lourenco Charles and Gahl, William and Boespflug-Tanguy,
Odile and Melberg, Atle and Hassin-Baer, Sharon and Cohen,
Oren S and Pjontek, Rastislav and Grau, Armin and Klopstock,
Thomas and Fogel, Brent and Meijer, Inge and Rouleau, Guy
and Bouchard, Jean-Pierre L and Ganapathiraju, Madhavi and
Vanderver, Adeline and Dahl, Niklas and Hobson, Grace and
Brusco, Alfredo and Brussino, Alessandro and Padiath, Quasar
Saleem},
title = {{A}nalysis of {LMNB}1 duplications in autosomal dominant
leukodystrophy provides insights into duplication mechanisms
and allele-specific expression.},
journal = {Human mutation},
volume = {34},
number = {8},
issn = {1059-7794},
address = {New York, NY [u.a.]},
publisher = {Wiley-Liss},
reportid = {DZNE-2020-03307},
pages = {1160-1171},
year = {2013},
abstract = {Autosomal dominant leukodystrophy (ADLD) is an adult onset
demyelinating disorder that is caused by duplications of the
lamin B1 (LMNB1) gene. However, as only a few cases have
been analyzed in detail, the mechanisms underlying LMNB1
duplications are unclear. We report the detailed molecular
analysis of the largest collection of ADLD families studied,
to date. We have identified the minimal duplicated region
necessary for the disease, defined all the duplication
junctions at the nucleotide level and identified the first
inverted LMNB1 duplication. We have demonstrated that the
duplications are not recurrent; patients with identical
duplications share the same haplotype, likely inherited from
a common founder and that the duplications originated from
intrachromosomal events. The duplication junction sequences
indicated that nonhomologous end joining or
replication-based mechanisms such fork stalling and template
switching or microhomology-mediated break induced repair are
likely to be involved. LMNB1 expression was increased in
patients' fibroblasts both at mRNA and protein levels and
the three LMNB1 alleles in ADLD patients show equal
expression, suggesting that regulatory regions are
maintained within the rearranged segment. These results have
allowed us to elucidate duplication mechanisms and provide
insights into allele-specific LMNB1 expression levels.},
keywords = {Adult / Base Sequence / Chromosome Breakpoints /
Comparative Genomic Hybridization / DNA: chemistry / DNA:
genetics / Gene Duplication / Humans / Lamin Type B:
genetics / Lamin Type B: metabolism / Molecular Sequence
Data / Nucleic Acid Conformation / Pelizaeus-Merzbacher
Disease: genetics / Pelizaeus-Merzbacher Disease: metabolism
/ RNA, Messenger: genetics / RNA, Messenger: metabolism /
Lamin Type B (NLM Chemicals) / RNA, Messenger (NLM
Chemicals) / lamin B1 (NLM Chemicals) / DNA (NLM Chemicals)},
cin = {AG Levin},
ddc = {610},
cid = {I:(DE-2719)1111016},
pnm = {344 - Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:23649844},
pmc = {pmc:PMC3714349},
doi = {10.1002/humu.22348},
url = {https://pub.dzne.de/record/136985},
}