Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression
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 analysi...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
3 May 2013
|
| In: |
Human mutation
Year: 2013, Volume: 34, Issue: 8, Pages: 1160-1171 |
| ISSN: | 1098-1004 |
| DOI: | https://doi.org/10.1002/humu.22348 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/https://doi.org/10.1002/humu.22348 Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.22348 
|
| Author Notes: | Elisa Giorgio, Harshvardhan Rolyan, Laura Kropp, Anish Baswanth Chakka, Svetlana Yatsenko, Eleonora Di Gregorio, Daniela Lacerenza, Giovanna Vaula, Flavia Talarico, Paola Mandich, Camilo Toro, Eleonore Eymard Pierre, Pierre Labauge, Sabina Capellari, Pietro Cortelli, Filippo Pinto Vairo, Diego Miguel, Danielle Stubbolo, Lourenco Charles Marques, William Gahl, Odile Boespflug‐Tanguy, Atle Melberg, Sharon Hassin‐Baer, Oren S. Cohen, Rastislav Pjontek, Armin Grau, Thomas Klopstock, Brent Fogel, Inge Meijer, Guy Rouleau, Jean-Pierre L. Bouchard, Madhavi Ganapathiraju, Adeline Vanderver, Niklas Dahl, Grace Hobson, Alfredo Brusco, Alessandro Brussino, and Quasar Saleem Padiath |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1751588327 | ||
| 003 | DE-627 | ||
| 005 | 20230615083515.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 210317s2013 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/humu.22348 |2 doi | |
| 035 | |a (DE-627)1751588327 | ||
| 035 | |a (DE-599)KXP1751588327 | ||
| 035 | |a (OCoLC)1341398970 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Giorgio, Elisa |e VerfasserIn |0 (DE-588)1229520007 |0 (DE-627)1751586553 |4 aut | |
| 245 | 1 | 0 | |a Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression |c Elisa Giorgio, Harshvardhan Rolyan, Laura Kropp, Anish Baswanth Chakka, Svetlana Yatsenko, Eleonora Di Gregorio, Daniela Lacerenza, Giovanna Vaula, Flavia Talarico, Paola Mandich, Camilo Toro, Eleonore Eymard Pierre, Pierre Labauge, Sabina Capellari, Pietro Cortelli, Filippo Pinto Vairo, Diego Miguel, Danielle Stubbolo, Lourenco Charles Marques, William Gahl, Odile Boespflug‐Tanguy, Atle Melberg, Sharon Hassin‐Baer, Oren S. Cohen, Rastislav Pjontek, Armin Grau, Thomas Klopstock, Brent Fogel, Inge Meijer, Guy Rouleau, Jean-Pierre L. Bouchard, Madhavi Ganapathiraju, Adeline Vanderver, Niklas Dahl, Grace Hobson, Alfredo Brusco, Alessandro Brussino, and Quasar Saleem Padiath |
| 264 | 1 | |c 3 May 2013 | |
| 300 | |a 12 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 17.03.2021 | ||
| 500 | |a Correction(s) for this article: Volume 35, Issue 1, Human Mutation, pages: 149-149 | ||
| 500 | |a First Published online: October 28, 2013 | ||
| 520 | |a 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. | ||
| 650 | 4 | |a ADLD | |
| 650 | 4 | |a duplication Alu | |
| 650 | 4 | |a FoSTeS | |
| 650 | 4 | |a Lamin B1 | |
| 650 | 4 | |a leukodystrophy | |
| 650 | 4 | |a MMBIR | |
| 650 | 4 | |a NHEJ | |
| 700 | 1 | |a Rolyan, Harshvardhan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kropp, Laura |e VerfasserIn |4 aut | |
| 700 | 1 | |a Chakka, Anish Baswanth |e VerfasserIn |4 aut | |
| 700 | 1 | |a Yatsenko, Svetlana |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gregorio, Eleonora Di |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lacerenza, Daniela |e VerfasserIn |4 aut | |
| 700 | 1 | |a Vaula, Giovanna |e VerfasserIn |4 aut | |
| 700 | 1 | |a Talarico, Flavia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mandich, Paola |e VerfasserIn |4 aut | |
| 700 | 1 | |a Toro, Camilo |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pierre, Eleonore Eymard |e VerfasserIn |4 aut | |
| 700 | 1 | |a Labauge, Pierre |e VerfasserIn |4 aut | |
| 700 | 1 | |a Capellari, Sabina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Cortelli, Pietro |e VerfasserIn |4 aut | |
| 700 | 1 | |a Vairo, Filippo Pinto |e VerfasserIn |4 aut | |
| 700 | 1 | |a Miguel, Diego |e VerfasserIn |4 aut | |
| 700 | 1 | |a Stubbolo, Danielle |e VerfasserIn |4 aut | |
| 700 | 1 | |a Marques, Lourenco Charles |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gahl, William |e VerfasserIn |4 aut | |
| 700 | 1 | |a Boespflug‐Tanguy, Odile |e VerfasserIn |4 aut | |
| 700 | 1 | |a Melberg, Atle |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hassin‐Baer, Sharon |e VerfasserIn |4 aut | |
| 700 | 1 | |a Cohen, Oren S. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pjontek, Rastislav |d 1984- |e VerfasserIn |0 (DE-588)1160276463 |0 (DE-627)1023428091 |0 (DE-576)505825007 |4 aut | |
| 700 | 1 | |a Grau, Armin J. |d 1959- |e VerfasserIn |0 (DE-588)1064028012 |0 (DE-627)812878906 |0 (DE-576)423571184 |4 aut | |
| 700 | 1 | |a Klopstock, Thomas* |e VerfasserIn |4 aut | |
| 700 | 1 | |a Fogel, Brent |e VerfasserIn |4 aut | |
| 700 | 1 | |a Meijer, Inge |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rouleau, Guy |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bouchard, Jean-Pierre L. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ganapathiraju, Madhavi |e VerfasserIn |4 aut | |
| 700 | 1 | |a Vanderver, Adeline |e VerfasserIn |4 aut | |
| 700 | 1 | |a Dahl, Niklas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hobson, Grace |e VerfasserIn |4 aut | |
| 700 | 1 | |a Brusco, Alfredo |e VerfasserIn |4 aut | |
| 700 | 1 | |a Brussino, Alessandro |e VerfasserIn |4 aut | |
| 700 | 1 | |a Padiath, Quasar Saleem |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Human mutation |d [Hoboken, NJ] : Wiley, 1992 |g 34(2013), 8, Seite 1160-1171 |h Online-Ressource |w (DE-627)306586193 |w (DE-600)1498165-8 |w (DE-576)250043572 |x 1098-1004 |7 nnas |a Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression |
| 773 | 1 | 8 | |g volume:34 |g year:2013 |g number:8 |g pages:1160-1171 |g extent:12 |a Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression |
| 856 | 4 | 0 | |u https://doi.org/https://doi.org/10.1002/humu.22348 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.22348 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20210317 | ||
| 993 | |a Article | ||
| 994 | |a 2013 | ||
| 998 | |g 1064028012 |a Grau, Armin J. |m 1064028012:Grau, Armin J. |d 50000 |e 50000PG1064028012 |k 0/50000/ |p 26 | ||
| 998 | |g 1160276463 |a Pjontek, Rastislav |m 1160276463:Pjontek, Rastislav |d 50000 |e 50000PP1160276463 |k 0/50000/ |p 25 | ||
| 999 | |a KXP-PPN1751588327 |e 3889996191 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"title":[{"title_sort":"Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression","title":"Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression"}],"person":[{"given":"Elisa","family":"Giorgio","role":"aut","roleDisplay":"VerfasserIn","display":"Giorgio, Elisa"},{"family":"Rolyan","given":"Harshvardhan","display":"Rolyan, Harshvardhan","roleDisplay":"VerfasserIn","role":"aut"},{"display":"Kropp, Laura","roleDisplay":"VerfasserIn","role":"aut","family":"Kropp","given":"Laura"},{"family":"Chakka","given":"Anish Baswanth","roleDisplay":"VerfasserIn","display":"Chakka, Anish Baswanth","role":"aut"},{"role":"aut","display":"Yatsenko, Svetlana","roleDisplay":"VerfasserIn","given":"Svetlana","family":"Yatsenko"},{"given":"Eleonora Di","family":"Gregorio","role":"aut","roleDisplay":"VerfasserIn","display":"Gregorio, Eleonora Di"},{"family":"Lacerenza","given":"Daniela","display":"Lacerenza, Daniela","roleDisplay":"VerfasserIn","role":"aut"},{"roleDisplay":"VerfasserIn","display":"Vaula, Giovanna","role":"aut","family":"Vaula","given":"Giovanna"},{"roleDisplay":"VerfasserIn","display":"Talarico, Flavia","role":"aut","family":"Talarico","given":"Flavia"},{"roleDisplay":"VerfasserIn","display":"Mandich, Paola","role":"aut","family":"Mandich","given":"Paola"},{"family":"Toro","given":"Camilo","display":"Toro, Camilo","roleDisplay":"VerfasserIn","role":"aut"},{"roleDisplay":"VerfasserIn","display":"Pierre, Eleonore Eymard","role":"aut","family":"Pierre","given":"Eleonore Eymard"},{"display":"Labauge, Pierre","roleDisplay":"VerfasserIn","role":"aut","family":"Labauge","given":"Pierre"},{"family":"Capellari","given":"Sabina","display":"Capellari, Sabina","roleDisplay":"VerfasserIn","role":"aut"},{"given":"Pietro","family":"Cortelli","role":"aut","display":"Cortelli, Pietro","roleDisplay":"VerfasserIn"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Vairo, Filippo Pinto","given":"Filippo Pinto","family":"Vairo"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Miguel, Diego","given":"Diego","family":"Miguel"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Stubbolo, Danielle","given":"Danielle","family":"Stubbolo"},{"display":"Marques, Lourenco Charles","roleDisplay":"VerfasserIn","role":"aut","family":"Marques","given":"Lourenco Charles"},{"given":"William","family":"Gahl","role":"aut","display":"Gahl, William","roleDisplay":"VerfasserIn"},{"given":"Odile","family":"Boespflug‐Tanguy","role":"aut","display":"Boespflug‐Tanguy, Odile","roleDisplay":"VerfasserIn"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Melberg, Atle","given":"Atle","family":"Melberg"},{"family":"Hassin‐Baer","given":"Sharon","display":"Hassin‐Baer, Sharon","roleDisplay":"VerfasserIn","role":"aut"},{"given":"Oren S.","family":"Cohen","role":"aut","roleDisplay":"VerfasserIn","display":"Cohen, Oren S."},{"family":"Pjontek","given":"Rastislav","roleDisplay":"VerfasserIn","display":"Pjontek, Rastislav","role":"aut"},{"given":"Armin J.","family":"Grau","role":"aut","display":"Grau, Armin J.","roleDisplay":"VerfasserIn"},{"display":"Klopstock, Thomas*","roleDisplay":"VerfasserIn","role":"aut","family":"Klopstock","given":"Thomas*"},{"roleDisplay":"VerfasserIn","display":"Fogel, Brent","role":"aut","family":"Fogel","given":"Brent"},{"family":"Meijer","given":"Inge","display":"Meijer, Inge","roleDisplay":"VerfasserIn","role":"aut"},{"display":"Rouleau, Guy","roleDisplay":"VerfasserIn","role":"aut","family":"Rouleau","given":"Guy"},{"display":"Bouchard, Jean-Pierre L.","roleDisplay":"VerfasserIn","role":"aut","family":"Bouchard","given":"Jean-Pierre L."},{"given":"Madhavi","family":"Ganapathiraju","role":"aut","roleDisplay":"VerfasserIn","display":"Ganapathiraju, Madhavi"},{"display":"Vanderver, Adeline","roleDisplay":"VerfasserIn","role":"aut","family":"Vanderver","given":"Adeline"},{"given":"Niklas","family":"Dahl","role":"aut","display":"Dahl, Niklas","roleDisplay":"VerfasserIn"},{"family":"Hobson","given":"Grace","roleDisplay":"VerfasserIn","display":"Hobson, Grace","role":"aut"},{"role":"aut","display":"Brusco, Alfredo","roleDisplay":"VerfasserIn","given":"Alfredo","family":"Brusco"},{"role":"aut","display":"Brussino, Alessandro","roleDisplay":"VerfasserIn","given":"Alessandro","family":"Brussino"},{"family":"Padiath","given":"Quasar Saleem","display":"Padiath, Quasar Saleem","roleDisplay":"VerfasserIn","role":"aut"}],"language":["eng"],"recId":"1751588327","type":{"bibl":"article-journal","media":"Online-Ressource"},"note":["Gesehen am 17.03.2021","Correction(s) for this article: Volume 35, Issue 1, Human Mutation, pages: 149-149","First Published online: October 28, 2013"],"id":{"eki":["1751588327"],"doi":["10.1002/humu.22348"]},"origin":[{"dateIssuedDisp":"3 May 2013","dateIssuedKey":"2013"}],"name":{"displayForm":["Elisa Giorgio, Harshvardhan Rolyan, Laura Kropp, Anish Baswanth Chakka, Svetlana Yatsenko, Eleonora Di Gregorio, Daniela Lacerenza, Giovanna Vaula, Flavia Talarico, Paola Mandich, Camilo Toro, Eleonore Eymard Pierre, Pierre Labauge, Sabina Capellari, Pietro Cortelli, Filippo Pinto Vairo, Diego Miguel, Danielle Stubbolo, Lourenco Charles Marques, William Gahl, Odile Boespflug‐Tanguy, Atle Melberg, Sharon Hassin‐Baer, Oren S. Cohen, Rastislav Pjontek, Armin Grau, Thomas Klopstock, Brent Fogel, Inge Meijer, Guy Rouleau, Jean-Pierre L. Bouchard, Madhavi Ganapathiraju, Adeline Vanderver, Niklas Dahl, Grace Hobson, Alfredo Brusco, Alessandro Brussino, and Quasar Saleem Padiath"]},"relHost":[{"origin":[{"dateIssuedDisp":"2024-","publisher":"Wiley ; Wiley-Liss ; Hindawi Limited","dateIssuedKey":"2024","publisherPlace":"[Hoboken, NJ] ; New York, NY [u.a.] ; London"}],"id":{"zdb":["1498165-8"],"eki":["306586193"],"doi":["10.1002/(ISSN)1098-1004"],"issn":["1098-1004"]},"physDesc":[{"extent":"Online-Ressource"}],"title":[{"title":"Human mutation","title_sort":"Human mutation"}],"type":{"bibl":"periodical","media":"Online-Ressource"},"note":["Gesehen am 27.01.2025"],"disp":"Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expressionHuman mutation","recId":"306586193","language":["eng"],"pubHistory":["1.1992 -"],"part":{"text":"34(2013), 8, Seite 1160-1171","volume":"34","extent":"12","year":"2013","pages":"1160-1171","issue":"8"}}],"physDesc":[{"extent":"12 S."}]} | ||
| SRT | |a GIORGIOELIANALYSISOF3201 | ||