leukodystrophies • POLR3-related leukodystrophy • hypomyelination • neurodegenerative diseases • molecular genetics
My research focuses on neurodegenerative disorders in children with a special focus on leukodystrophies, a group of inherited white matter diseases of the brain. My research team is investigating the clinical and imaging characteristics of these diseases along with their genetic causes. Recently, my colleagues and I discovered three genes responsible for causing a subset of leukodystrophies called POLR3-related leukodystrophies. To build on these key findings, my laboratory is working on the identification of new forms of leukodystrophies and on characterizing the newly described POLR3-related subset. Our research program is expanding to include perspectives from the study of epidemiology, natural history, and quality-of-life impacts, with the ultimate objective of improving care for children and families who face the serious challenges associated with this disease group.
Thiffault I, Wolf NI, Forget D, Guerrero K, Tran LT, Choquet K, Lavallée-Adam M, Poitras C, Brais B, Yoon G, Sztriha L, Webster RI, Timmann D, van de Warrenburg BP, Seeger J, Zimmermann A, Máté A, Goizet C, Fung E, van der Knaap MS, Fribourg S, Vanderver A, Simons C, Taft RJ, Yates III JR, Coulombe B, Bernard, G. Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III. Nat Commun. 2015 Jul 7;6:7623 PMID: 26151409.
Gutierrez M, Thiffault I, Guerrero K, Martos-Moreno GA, Tran LT, Benko W, van der Knaap MS, van Spaendonk RML, Wolf NI, Bernard G. Large exonic deletions in POLR3B gene cause POLR3-related leukodystrophy. Orphanet J Rare Dis. 2015 Jun 5;10(1):69. PMID: 26045207.
Parikh S, Bernard G, Leventer RJ, van der Knaap MS, Van Hove JL, Pizzino A, McNeill NH, Helman G, Simons C, Rizzo WB, Patterson MC, Vanderver A, Taft RJ, on behalf of the GLIA Consortium. A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephalopathies. Mol Genet Metab 2014 Dec 29. PMID: 25655951.
Wolf NI, Vanderver A, van Spaendonk RML, Schiffmann R, Brais B, Bugiani M, Sistermans EA, Catsman-Berrevoets C, Kros JM, Pinto PS, Pohl D, Tirupathi S, Strømme P, de Grauw T, Fribourg S, Demos M, Pizzino A, Naidu S, Guerrero K, van der Knaap MS, Bernard G; On behalf of the 4H Research Group. Clinical spectrum of 4H leukodystrophy caused by POLR3A and POLR3B mutations. Neurology 2014 Nov 18;83(21):1898-905 PMID: 25339210.
Tétreault M*, Choquet K*, Orcesi S, Tonduti D, Balottin U, Teichmann M, Fribourg S, Schiffmann R, Brais B, Vanderver A, Bernard G. Recessive mutations in POLR3B encoding the second largest subunit of Pol III cause a rare hypomyelinating leukodystrophy, Am J Hum Genet 2011 Nov 11;89(5):652-655 [Epub 2011 Oct 27]. PMID: 22036172.