Leukodystrophies and genetically-determined leukoencephalopathies are a group of rare genetic diseases affecting previously healthy individuals. Most of these diseases are degenerative and affect primarily children. Leukodystrophies and genetically-determined leukoencephalopathies are caused by abnormalities in myelin or white matter, which is involved in protecting neurons, or nerve cells, and ensure the rapid conduction of nerve impulses. Dr. Geneviève Bernard’s research program addresses the main knowledge gaps for this group of diseases and includes the following broad aims: (1) clinical and radiological characterization of leukodystrophies, (2) description of their natural history, (3) description of their impact on patients and their families (quality of life, stress), (4) identification of new causal genes, (5) study of their pathophysiology, (7) development of novel therapeutic strategies and, (8) development and participation in future therapeutic trials.
Dr. Geneviève Bernard received her Medical Degree (2002) and Master’s degree in Neurosciences (2003) from Université de Montréal. She completed her residency in Pediatric Neurology at McGill University (2008) and her fellowship in Neurogenetics and Movement Disorders at Université de Montréal (2011) under the supervision of Pr. Bernard Brais, Pr. Guy A Rouleau and Dr. Sylvain Chouinard. She started her career as an independent investigator and pediatric neurologist in October 2011 at the Montreal Children’s Hospital of the McGill University Health Center (MUHC) and MUHC Research Institute. She is currently an Associate Professor at McGill University, in the Departments of Neurology and Neurosurgery, Pediatrics and Human Genetics. She is a member of the Medical Genetics Division at the MUHC. Dr. Bernard and her team, together with her international collaborators, discovered the three genes responsible for 4H leukodystrophy and published, in collaboration with Dr. Nicole Wolf and numerous international collaborators, the largest clinical, radiological and genetic characterization study on this disorder. Dr. Bernard published more than 75 peer-reviewed publications, including some in high impact factor journals, several book chapters and numerous abstracts. She is the Canadian representative on several international consortia, including the Global Leukodystrophy InitiAtive (GLIA), ALD connect and the tRNA synthetases disorders research consortia.
1) Mendes MI^, Gutierrez Salazar M^, Guerrero K^, Thiffault I, Salomons GS, Gauquelin L, Tran LT, Forget D, Gauthier MS, Waisfisz Q, Smith DEC, Simons C, van der Knaap MS, Marquardt I, Lemes A, Mierzewska H, Weschke B, Koehler W, Coulombe B, Wolf NI^^, Bernard G^^. Bi-allelic mutations in EPRS, encoding the glutamyl-prolyl-aminoacyl-tRNA synthetase, cause a Hypomyelinating Leukodystrophy. Am J Hum Genet 2018, Apr 5;102(4):676-684. doi: 10.1016/j.ajhg.2018.02.011. Epub 2018 Mar 22. (PMID: 29576217) IF: 9.025*
2) Adang LA, Sherbini O, Ball L, Bloom M, Darbari A, Amartino H, Divito D, Eichler F, Escolar M, Evans SH, Fatemi A, Fraser J, Hollowell L, Jaffe N, Joseph C, Karpinski M, Keller S, Maddock R, Mancilla E, McClary B, Mertz J, Morgart K, Langan T, Leventer R, Parikh S, Pizzino A, Prange E, Renaud D, Rizzo W, Shapiro J, Suhr D, Suhr T, Tonduti D, Waggoner J, Waldman A, Wolf NI, Zerem A, Bonkowsky JL, Bernard G^^, van Haren K^^, Vanderver A^^, on behalf of the Global Leukodystrophy Initiative (GLIA) Consortium. Revised Consensus Statement on the Preventive and Symptomatic Care of Patients with Leukodystrophies. Mol Genet Metab. 2017 Sep;122(1-2):18-32. Epub 2017 Aug 20. (PMID: 28863857) IF: 3.769
3) La Piana R^, Cayami FK^, Tran LT, Guerrero K, van Spaendonk RML, Õunap K, Pajusalu S, Prokisch H, Wassmer E, Timmann D, Mierzewska H, Poll-Thé BT, Patel C , Cox H, Atik T, Onay H, Ozkınay F, Vanderver A, van der Knaap MS, Wolf NI^^, Bernard G^^. Diffuse hypomyelination is not obligate for POLR3-related disorders. Neurology 2016 Apr 26;86(17):1622-6 (PMID:27029625). IF: 8.286 *
4) 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. Nature Commun. 2015 Jul 7;6:7623 (PMID: 26151409). IF: 11.470
5) 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) IF: 8.286
6) Pouwels PJW^, Vanderver A^, Bernard G^, Wolf N^, Dreha-Kulczewski, Deoni S, Bertini E, Kohlschütter, Richardson W, ffrench-Constant C, Kölher W^^, Rowitch D^^, Barkovich AJ^^ Hypomyelinating leukodystrophies: Progress and prospects in translational research. Ann Neurol. 2014 Jul;76(1):5-19. IF: 11.91
7) Daoud H^, Tetreault M^, Gibson W, Guerrero K, Cohen A, Gburek-Augustat J, Synofzik M, Brais B, Stevens C, Sanchez-Carpintero R, Goizet C, Naidu S, Vanderver A, Bernard G. Mutations in POLR3A and POLR3B are a major cause of hypomyelinating leukodystrophies. J Med Genet. 2013 Mar;50(3):194-7. Epub 2013 Jan 25. (PMID: 23355746) IF: 6.335 *
8) 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. (PMID: 22036172) IF: 11.202 *
9) Bernard G, Chouery E, Putorti ML, Tétreault M, Takanohashi A, Carosso G, Clément I, Boespflug-Tanguy O, Rodriguez D, Delague V, Abou Ghoch J, Jalkh N, Dorboz I, Fribourg S, Teichmann M, Megarbane A, Schiffmann R, Vanderver A, Brais B. Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy. Am J Hum Genet 2011;89(3):415-423. (PIMD: 21855841) IF: 11.202