Current Funding Opportunities
We are excited to be working in partnership with the Orphan Disease Center at the University of Pennsylvania to fund up to two 1-year grants of $50,000 each. The ADLD Center will be seeking grant applications for multidisciplinary teams of scientists that aim to further progress our understanding of the disease, the available therapeutic options, and investigating strategies to establish outcome measurements.
Scientific Resources
Publications about clinical diagnosis, management and treatment of ADLD, LMNB1 mutations, and LaminB1 can be found below:
Alturkustani, M., Sharma, M., Hammond, R., & Ang, L. C. (2013). Adult-onset leukodystrophy: review of 3 clinicopathologic phenotypes and a proposed classification. J Neuropathol Exp Neurol, 72(11), 1090-1103. doi:10.1097/NEN.0000000000000008
Asahara, H., Yoshimura, T., Sada, S., Furuya, H., & Kobayashi, T. (1996). [A Japanese family with probably autosomal dominant adult-onset leukodystrophy]. Rinsho Shinkeigaku, 36(8), 968-972. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/8958750
Bartoletti-Stella, A., Gasparini, L., Giacomini, C., Corrado, P., Terlizzi, R., Giorgio, E., . . . Capellari, S. (2015). Messenger RNA processing is altered in autosomal dominant leukodystrophy. Hum Mol Genet, 24(10), 2746-2756. doi:10.1093/hmg/ddv034
Brussino, A., Vaula, G., Cagnoli, C., Mauro, A., Pradotto, L., Daniele, D., . . . Brusco, A. (2009). A novel family with Lamin B1 duplication associated with adult-onset leucoencephalopathy. J Neurol Neurosurg Psychiatry, 80(2), 237-240. doi:10.1136/jnnp.2008.147330
Brussino, A., Vaula, G., Cagnoli, C., Panza, E., Seri, M., Di Gregorio, E., . . . Brusco, A. (2010). A family with autosomal dominant leukodystrophy linked to 5q23.2-q23.3 without lamin B1 mutations. Eur J Neurol, 17(4), 541-549. doi:10.1111/j.1468-1331.2009.02844.x
Columbaro, M., Mattioli, E., Maraldi, N. M., Ortolani, M., Gasparini, L., D’Apice, M. R., . . . Lattanzi, G. (2013). Oct-1 recruitment to the nuclear envelope in adult-onset autosomal dominant leukodystrophy. Biochim Biophys Acta, 1832(3), 411-420. doi:10.1016/j.bbadis.2012.12.006
Dai, Y., Ma, Y., Li, S., Banerjee, S., Liang, S., Liu, Q., . . . Jin, L. (2017). An LMNB1 Duplication Caused Adult-Onset Autosomal Dominant Leukodystrophy in Chinese Family: Clinical Manifestations, Neuroradiology and Genetic Diagnosis. Front Mol Neurosci, 10, 215. doi:10.3389/fnmol.2017.00215
Di Donato, I., Banchi, S., Federico, A., & Dotti, M. T. (2014). Adult-Onset Genetic Leukoencephalopathies. Focus on the More Recently Defined Forms. Curr Mol Med, 14(8), 944-958. doi:10.2174/1566524014666141010130545
Di Donato, I., Dotti, M. T., & Federico, A. (2014). Update on several/certain adult-onset genetic leukoencephalopathies: clinical signs and molecular confirmation. J Alzheimers Dis, 42 Suppl 3, S27-35. doi:10.3233/JAD-141026
Dos Santos, M. M., Grond-Ginsbach, C., Aksay, S. S., Chen, B., Tchatchou, S., Wolf, N. I., . . . Grau, A. J. (2012). Adult-onset autosomal dominant leukodystrophy due to LMNB1 gene duplication. J Neurol, 259(3), 579-581. doi:10.1007/s00415-011-6225-4
Dreesen, O., Ong, P. F., Chojnowski, A., & Colman, A. (2013). The contrasting roles of lamin B1 in cellular aging and human disease. Nucleus, 4(4), 283-290. doi:10.4161/nucl.25808
Eldridge, R., Anayiotos, C. P., Schlesinger, S., Cowen, D., Bever, C., Patronas, N., & McFarland, H. (1984). Hereditary adult-onset leukodystrophy simulating chronic progressive multiple sclerosis. N Engl J Med, 311(15), 948-953. doi:10.1056/NEJM198410113111504
Ferrera, D., Canale, C., Marotta, R., Mazzaro, N., Gritti, M., Mazzanti, M., . . . Gasparini, L. (2014). Lamin B1 overexpression increases nuclear rigidity in autosomal dominant leukodystrophy fibroblasts. FASEB J, 28(9), 3906-3918. doi:10.1096/fj.13-247635
Finnsson, J., Lubberink, M., Savitcheva, I., Fallmar, D., Melberg, A., Kumlien, E., & Raininko, R. (2019). Glucose metabolism in the brain in LMNB1-related autosomal dominant leukodystrophy. Acta Neurol Scand, 139(2), 135-142. doi:10.1111/ane.13024
Finnsson, J., Sundblom, J., Dahl, N., Melberg, A., & Raininko, R. (2015). LMNB1-related autosomal-dominant leukodystrophy: Clinical and radiological course. Ann Neurol, 78(3), 412-425. doi:10.1002/ana.24452
Giacomini, C., Mahajani, S., Ruffilli, R., Marotta, R., & Gasparini, L. (2016). Lamin B1 protein is required for dendrite development in primary mouse cortical neurons. Mol Biol Cell, 27(1), 35-47. doi:10.1091/mbc.E15-05-0307
Giorgio, E., Lorenzati, M., Rivetti di Val Cervo, P., Brussino, A., Cernigoj, M., Della Sala, E., . . . Brusco, A. (2019). Allele-specific silencing as treatment for gene duplication disorders: proof-of-principle in autosomal dominant leukodystrophy. Brain, 142(7), 1905-1920. doi:10.1093/brain/awz139
Giorgio, E., Rolyan, H., Kropp, L., Chakka, A. B., Yatsenko, S., Di Gregorio, E., . . . Padiath, Q. S. (2013). Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression. Hum Mutat, 34(8), 1160-1171. doi:10.1002/humu.22348
Hutchison, C. J. (2014). B-type lamins in health and disease. Semin Cell Dev Biol, 29, 158-163. doi:10.1016/j.semcdb.2013.12.012
Jaklin, C., Heiliger, K., Hempel, M., Sollacher, D., Cohen, M., Makowski, C. C., . . . Oexle, K. (2012). Cryptic del/dup aberration of 60.6 Mb at 5q15-5q23.3 predicting adult-onset leukodystrophy. Eur J Med Genet, 55(10), 568-572. doi:10.1016/j.ejmg.2012.06.010
Koeppen, A. H. (2001). Re.: Clinical, radiological and pathological findings in an autosomal dominant leukodystrophy. J Neurol Sci, 187(1-2), 107, 109. doi:10.1016/s0022-510x(01)00535-4
Labauge, P., Fogli, A., Castelnovo, G., Le Bayon, A., Horzinski, L., Nicoli, F., . . . Rodriguez, D. (2005). Dominant form of vanishing white matter-like leukoencephalopathy. Ann Neurol, 58(4), 634-639. doi:10.1002/ana.20573
Leombruni, S., Vaula, G., Coletti Moja, M., Bergui, M., Bergamini, L., & Quattrocolo, G. (1998). Neurophysiological study in an Italian family with autosomal dominant late-onset leukodystrophy. Electromyogr Clin Neurophysiol, 38(3), 131-135. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/9637937
Lin, S. T., & Fu, Y. H. (2009). miR-23 regulation of lamin B1 is crucial for oligodendrocyte development and myelination. Dis Model Mech, 2(3-4), 178-188. doi:10.1242/dmm.001065
Lo Martire, V., Alvente, S., Bastianini, S., Berteotti, C., Bombardi, C., Calandra-Buonaura, G., . . . Silvani, A. (2018). Mice overexpressing lamin B1 in oligodendrocytes recapitulate the age-dependent motor signs, but not the early autonomic cardiovascular dysfunction of autosomal-dominant leukodystrophy (ADLD). Exp Neurol, 301(Pt A), 1-12. doi:10.1016/j.expneurol.2017.12.006
Marklund, L., Melin, M., Melberg, A., Giedraitis, V., & Dahl, N. (2006). Adult-onset autosomal dominant leukodystrophy with autonomic symptoms restricted to 1.5 Mbp on chromosome 5q23. Am J Med Genet B Neuropsychiatr Genet, 141B(6), 608-614. doi:10.1002/ajmg.b.30342
Meijer, I. A., Simoes-Lopes, A. A., Laurent, S., Katz, T., St-Onge, J., Verlaan, D. J., . . . Rouleau, G. A. (2008). A novel duplication confirms the involvement of 5q23.2 in autosomal dominant leukodystrophy. Arch Neurol, 65(11), 1496-1501. doi:10.1001/archneur.65.11.1496
Melberg, A., Hallberg, L., Kalimo, H., & Raininko, R. (2006). MR characteristics and neuropathology in adult-onset autosomal dominant leukodystrophy with autonomic symptoms. AJNR Am J Neuroradiol, 27(4), 904-911. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/16611789
Mezaki, N., Miura, T., Ogaki, K., Eriguchi, M., Mizuno, Y., Komatsu, K., . . . Ikeuchi, T. (2018). Duplication and deletion upstream of LMNB1 in autosomal dominant adult-onset leukodystrophy. Neurol Genet, 4(6), e292. doi:10.1212/NXG.0000000000000292
Nahhas, N., Sabet Rasekh, P., Vanderver, A., & Padiath, Q. (2016). Autosomal Dominant Leukodystrophy with Autonomic Disease. In M. P. Adam, H. H. Ardinger, R. A. Pagon, S. E. Wallace, L. J. H. Bean, K. Stephens, & A. Amemiya (Eds.), GeneReviews((R)). Seattle (WA).
Nmezi, B., Giorgio, E., Raininko, R., Lehman, A., Spielmann, M., Koenig, M. K., . . . Padiath, Q. S. (2019). Genomic deletions upstream of lamin B1 lead to atypical autosomal dominant leukodystrophy. Neurol Genet, 5(1), e305. doi:10.1212/NXG.0000000000000305
Padiath, Q. S. (2016). Lamin B1 mediated demyelination: Linking Lamins, Lipids and Leukodystrophies. Nucleus, 7(6), 547-553. doi:10.1080/19491034.2016.1260799
Padiath, Q. S. (2019). Autosomal Dominant Leukodystrophy: A Disease of the Nuclear Lamina. Front Cell Dev Biol, 7, 41. doi:10.3389/fcell.2019.00041
Padiath, Q. S., & Fu, Y. H. (2010). Autosomal dominant leukodystrophy caused by lamin B1 duplications a clinical and molecular case study of altered nuclear function and disease. Methods Cell Biol, 98, 337-357. doi:10.1016/S0091-679X(10)98014-X
Padiath, Q. S., Saigoh, K., Schiffmann, R., Asahara, H., Yamada, T., Koeppen, A., . . . Fu, Y. H. (2006). Lamin B1 duplications cause autosomal dominant leukodystrophy. Nat Genet, 38(10), 1114-1123. doi:10.1038/ng1872
Pedroso, J. L., Munford, V., Bastos, A. U., Castro, L. P., Marussi, V. H. R., Silva, G. S., . . . Barsottini, O. G. (2017). LMNB1 mutation causes cerebellar involvement and a genome instability defect. J Neurol Sci, 379, 249-252. doi:10.1016/j.jns.2017.06.027
Potic, A., Pavlovic, A. M., Uziel, G., Kozic, D., Ostojic, J., Rovelli, A., . . . Taroni, F. (2013). Adult-onset autosomal dominant leukodystrophy without early autonomic dysfunctions linked to lamin B1 duplication: a phenotypic variant. J Neurol, 260(8), 2124-2129. doi:10.1007/s00415-013-6958-3
Ptacek, L. J., Fu, Y. H., & Koeppen, A. (2006). The dominant form of vanishing white matter-like leukoencephalopathy represents autosomal dominant leukodystrophy. Ann Neurol, 59(2), 434. doi:10.1002/ana.20773
Robinson, A., Partridge, D., Malhas, A., De Castro, S. C., Gustavsson, P., Thompson, D. N., . . . Greene, N. D. (2013). Is LMNB1 a susceptibility gene for neural tube defects in humans? Birth Defects Res A Clin Mol Teratol, 97(6), 398-402. doi:10.1002/bdra.23141
Rolyan, H., Tyurina, Y. Y., Hernandez, M., Amoscato, A. A., Sparvero, L. J., Nmezi, B. C., . . . Padiath, Q. S. (2015). Defects of Lipid Synthesis Are Linked to the Age-Dependent Demyelination Caused by Lamin B1 Overexpression. J Neurosci, 35(34), 12002-12017. doi:10.1523/JNEUROSCI.1668-15.2015
Schuster, J., Sundblom, J., Thuresson, A. C., Hassin-Baer, S., Klopstock, T., Dichgans, M., . . . Dahl, N. (2011). Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms. Neurogenetics, 12(1), 65-72. doi:10.1007/s10048-010-0269-y
Tagawa, A., Ono, S., Inoue, K., Hosoi, N., Kaneda, K., Suzuki, M., . . . Shimizu, N. (2001). A new familial adult-onset leukodystrophy manifesting as cerebellar ataxia and dementia. J Neurol Sci, 183(1), 47-55. doi:10.1016/s0022-510x(00)00472-x
Zanigni, S., Terlizzi, R., Tonon, C., Testa, C., Manners, D. N., Capellari, S., . . . Lodi, R. (2015). Brain magnetic resonance metabolic and microstructural changes in adult-onset autosomal dominant leukodystrophy. Brain Res Bull, 117, 24-31. doi:10.1016/j.brainresbull.2015.07.002
Zhang, Y., Li, J., Bai, R., Wang, J., Peng, T., Chen, L., . . . Lu, H. (2019). LMNB1-Related Adult-Onset Autosomal Dominant Leukodystrophy Presenting as Movement Disorder: A Case Report and Review of the Literature. Front Neurosci, 13, 1030. doi:10.3389/fnins.2019.01030