Overview

The main focus of my work is the investigation of the complex series of events at the cellular and tissue level that are at play in the evolution and of genetic disease. It is hoped that an understanding of disease at this level will result in the development of specific forms of therapy for rare genetic disease. My group has chosen to focus on a series of devastating progressive disorders termed lysosomal storage diseases.

Publications

12year follow up of enzyme-replacement therapy in two siblings with attenuated mucopolysaccharidosis I: The important role of early treatment
BMC Medical Genetics
Gabrielli, O. and Clarke, L.A. and Ficcadenti, A. and Santoro, L. and Zampini, L. and Volpi, N. and Coppa, G.V.
DOI: 10.1186/s12881-016-0284-4
2016

Implementing evidence-driven individualized treatment plans within Morquio A Syndrome
Molecular Genetics and Metabolism
Clarke, L.A. and Harmatz, P. and Fong, E.W.
DOI: 10.1016/j.ymgme.2015.12.157
2016

Is it Fabry disease?
Genetics in Medicine
Schiffmann, R. and Fuller, M. and Clarke, L.A. and Aerts, J.M.F.G.
DOI: 10.1038/gim.2016.55
2016

Mucopolysaccharidosis Type I Newborn Screening: Best Practices for Diagnosis and Management
Journal of Pediatrics
Clarke, L.A. and Atherton, A.M. and Burton, B.K. and Day-Salvatore, D.L. and Kaplan, P. and Leslie, N.D. and Scott, C.R. and Stockton, D.W. and Thomas, J.A. and Muenzer, J.
DOI: 10.1016/j.jpeds.2016.11.036
2016

The clinical spectrum and pathophysiology of skeletal complications in lysosomal storage disorders
Best Practice and Research: Clinical Endocrinology and Metabolism
Clarke, L.A. and Hollak, C.E.M.
DOI: 10.1016/j.beem.2014.08.010
2015

Characterization of early disease status in treatment-naive male paediatric patients with fabry disease enrolled in a randomized clinical trial
PLoS ONE
Wijburg, F.A., Bénichou, B., Bichet, D.G., Clarke, L.A., Dostalova, G., Fainboim, A., Fellgiebel, A., Forcelini, C., Haack, K.A., Hopkin, R.J., Mauer, M., Najafian, B., Scott, C.R., Shankar, S.P., Thurberg, B.L., Tøndel, C., Tylki-Szymanska, A., Ramaswami, U.
DOI: 10.1371/journal.pone.0124987
2015

Extracellular matrix disruption is an early event in the pathogenesis of skeletal disease in mucopolysaccharidosis I
Molecular Genetics and Metabolism
Heppner, J.M. and Zaucke, F. and Clarke, L.A.
DOI: 10.1016/j.ymgme.2014.09.012
2015

Mucopolysaccharidosis IVA (Morquio A syndrome) and VI (Maroteaux-Lamy syndrome): Under-recognized and challenging to diagnose
Skeletal Radiology
Lachman, R.S. and Burton, B.K. and Clarke, L.A. and Hoffinger, S. and Ikegawa, S. and Jin, D.-K. and Kano, H. and Kim, O.-H. and Lampe, C. and Mendelsohn, N.J. and Shediac, R. and Tanpaiboon, P. and White, K.K.
DOI: 10.1007/s00256-013-1797-y
2014

Biomarkers
Advances in Gaucher Disease: Basic and Clinical Perspectives
Clarke, L.
DOI: 10.2217/EBO.12.189
2013

Fetal progeria: Prenatal sonographic findings in petty syndrome
Journal of Ultrasound in Medicine
Pugash, D. and Schrader, K.A. and Dunham, C.P. and Popescu, O.-E. and Sargent, M.A. and Lehman, A.M. and Yong, S.L. and Clarke, L.A.
DOI: 10.7863/ultra.32.5.881
2013

Transgenic mice expressing human glucocerebrosidase variants: Utility for the study of Gaucher disease
Blood Cells, Molecules, and Diseases
Sanders, A. and Hemmelgarn, H. and Melrose, H.L. and Hein, L. and Fuller, M. and Clarke, L.A.
DOI: 10.1016/j.bcmd.2013.03.006
2013

Capturing phenotypic heterogeneity in MPS I: Results of an international consensus procedure
Orphanet Journal of Rare Diseases
de Ru, M.H. and Teunissen, Q.G.A. and van der Lee, J.H. and Beck, M. and Bodamer, O.A. and Clarke, L.A. and Hollak, C.E. and Lin, S.-P. and Munoz Rojas, M.-V. and Pastores, G.M. and Raiman, J.A. and Scarpa, M. and Treacy, E.P. and Tylki-Szymanska, A. and Wraith, E. and Zeman, J. and Wijburg, F.A.
DOI: 10.1186/1750-1172-7-22
2012

Capturing phenotypic heterogeneity in MPS I: Results of an international consensus procedure
Orphanet Journal of Rare Diseases
De Ru, M.H. and Teunissen, Q.G.A. and Van Der Lee, J.H. and Beck, M. and Bodamer, O.A. and Clarke, L.A. and Hollak, C.E. and Lin, S.-P. and Rojas, M.-V.M. and Pastores, G.M. and Raiman, J.A. and Scarpa, M. and Treacy, E.P. and Tylki-Szymanska, A. and Wraith, J.E. and Zeman, J. and Wijburg, F.A.
DOI: 10.1186/1750-1172-7-2222524701
2012

The role of enzyme replacement therapy in severe Hunter syndrome-an expert panel consensus
European Journal of Pediatrics
Muenzer, J. and Bodamer, O. and Burton, B. and Clarke, L. and Frenking, G.S. and Giugliani, R. and Jones, S. and Rojas, M.V.M. and Scarpa, M. and Beck, M. and Harmatz, P.
DOI: 10.1007/s00431-011-1606-3
2012

Longitudinal observations of serum heparin cofactor II-thrombin complex in treated Mucopolysaccharidosis i and II patients
Journal of Inherited Metabolic Disease
Clarke, L.A. and Hemmelgarn, H. and Colobong, K. and Thomas, A. and Stockler, S. and Casey, R. and Chan, A. and Fernoff, P. and Mitchell, J.
DOI: 10.1007/s10545-011-9369-6
2012

Biomarkers for the mucopolysaccharidoses: Discovery and clinical utility
Molecular Genetics and Metabolism
Clarke, L.A. and Winchester, B. and Giugliani, R. and Tylki-Szyma?ska, A. and Amartino, H.
DOI: 10.1016/j.ymgme.2012.05.003
2012

Production of a-L-iduronidase in maize for the potential treatment of a human lysosomal storage disease
Nature Communications
He, X. and Haselhorst, T. and Von Itzstein, M. and Kolarich, D. and Packer, N.H. and Gloster, T.M. and Vocadlo, D.J. and Clarke, L.A. and Qian, Y. and Kermode, A.R.
DOI: 10.1038/ncomms2070
2012

Production of active human glucocerebrosidase in seeds of Arabidopsis thaliana complex-glycan-deficient (cgl) plants
Glycobiology
He, X. and Galpin, J.D. and Tropak, M.B. and Mahuran, D. and Haselhorst, T. and Von Itzstein, M. and Kolarich, D. and Packer, N.H. and Miao, Y. and Jiang, L. and Grabowski, G.A. and Clarke, L.A. and Kermode, A.R.
DOI: 10.1093/glycob/cwr157
2012

Left ventricular aneurysm in an adult patient with mucopolysaccharidosis type I: Comment on pathogenesis of a novel complication
Molecular Genetics and Metabolism
Cabrera, G.H., Fernández, I., Dominguez, M., Clarke, L.A.
DOI: 10.1016/j.ymgme.2012.06.001
2012

Pathogenesis of skeletal and connective tissue involvement in the mucopolysaccharidoses: Glycosaminoglycan storage is merely the instigator
Rheumatology
Clarke, L.A.
DOI: 10.1093/rheumatology/ker395
2011

Exome sequencing identifies SMAD3 mutations as a cause of familial thoracic aortic aneurysm and dissection with intracranial and other arterial aneurysms
Circulation Research
Regalado, E.S. and Guo, D.-C. and Villamizar, C. and Avidan, N. and Gilchrist, D. and McGillivray, B. and Clarke, L. and Bernier, F. and Santos-Cortez, R.L. and Leal, S.M. and Bertoli-Avella, A.M. and Shendure, J. and Rieder, M.J. and Nickerson, D.A. and Milewicz, D.M.
DOI: 10.1161/CIRCRESAHA.111.248161
2011

Urolithiasis and hepatotoxicity are linked to the anion transporter Sat1 in mice
Journal of Clinical Investigation
Dawson, P.A. and Russell, C.S. and Lee, S. and McLeay, S.C. and Van Dongen, J.M. and Cowley, D.M. and Clarke, L.A. and Markovich, D.
DOI: 10.1172/JCI31474
2010

Imaging of enzyme replacement therapy using PET
Proceedings of the National Academy of Sciences of the United States of America
Phenix, C.P. and Rempel, B.P. and Colobong, K. and Doudet, D.J. and Adam, M.J. and Clarke, L.A. and Withers, S.G.
DOI: 10.1073/pnas.1003247107
2010

Characterization of an MPS I-H knock-in mouse that carries a nonsense mutation analogous to the human IDUA-W402X mutation
Molecular Genetics and Metabolism
Wang, D. and Shukla, C. and Liu, X. and Schoeb, T.R. and Clarke, L.A. and Bedwell, D.M. and Keeling, K.M.
DOI: 10.1016/j.ymgme.2009.08.002
2010

Enzyme-replacement therapy in a 5-month-old boy with attenuated presymptomatic MPS I: 5-year follow-up
Pediatrics
Gabrielli, O. and Clarke, L.A. and Bruni, S. and Coppa, G.V.
DOI: 10.1542/peds.2009-1728
2010

Corrigendum to "Characterization of an MPS I-H knock-in mouse that carries a nonsense mutation analogous to the human IDUA-W402X mutation" [Mol. Genet. Metab. 99 (2010) 62-71] (DOI:10.1016/j.ymgme.2009.08.002)
Molecular Genetics and Metabolism
Wang, D. and Shukla, C. and Liu, X. and Schoeb, T.R. and Clarke, L.A. and Bedwell, D.M. and Keeling, K.M.
DOI: 10.1016/j.ymgme.2009.12.013
2010

Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I
Pediatrics
Clarke, L.A. and Wraith, J.E. and Beck, M. and Kolodny, E.H. and Pastores, G.M. and Muenzer, J. and Rapoport, D.M. and Berger, K.I. and Sidman, M. and Kakkis, E.D. and Cox, G.F.
DOI: 10.1542/peds.2007-3847
2009

Production and characterization of soluble human lysosomal enzyme a-iduronidase with high activity from culture media of transgenic tobacco BY-2 cells
Plant Science
Fu, L.H. and Miao, Y. and Lo, S.W. and Seto, T.C. and Sun, S.S.M. and Xu, Z.-F. and Clemens, S. and Clarke, L.A. and Kermode, A.R. and Jiang, L.
DOI: 10.1016/j.plantsci.2009.08.016
2009

Glycosaminoglycan-mediated loss of cathepsin K collagenolytic activity in MPS I contributes to osteoclast and growth plate abnormalities
American Journal of Pathology
Wilson, S., Hashamiyan, S., Clarke, L., Saftig, P., Mort, J., Dejica, V.M., Brömme, D.
DOI: 10.2353/ajpath.2009.090211
2009

The mucopolysaccharidoses: A success of molecular medicine (Expert Reviews in Molecular Medicine (2008) 10, (e1) DOI: 10.1017/S1462399408000550)
Expert Reviews in Molecular Medicine
Clarke, L.A.
DOI: 10.1017/S1462399409001185
2009

Intracranial calcification after cord blood neonatal transplantation for Krabbe disease
Neuropediatrics
Lehman, A.M. and Schultz, K.R. and Poskitt, K. and Bjornson, B. and Keyes, R. and Waters, P.J. and Clarke, L.A. and Everett, R. and McConnell, D. and Stockler, S.
DOI: 10.1055/s-0029-1243189
2009

Mucopolysaccharidosis I: Management and treatment guidelines
Pediatrics
Muenzer, J. and Wraith, J.E. and Clarke, L.A.
DOI: 10.1542/peds.2008-0416
2009

The mucopolysaccharidoses: A success of molecular medicine
Expert Reviews in Molecular Medicine
Clarke, L.A.
DOI: 10.1017/S1462399408000550
2008

Heparin cofactor II-thrombin complex: A biomarker of MPS disease
Molecular Genetics and Metabolism
Randall, D.R. and Colobong, K.E. and Hemmelgarn, H. and Sinclair, G.B. and Hetty, E. and Thomas, A. and Bodamer, O.A. and Volkmar, B. and Fernhoff, P.M. and Casey, R. and Chan, A.K. and Mitchell, G. and Stockler, S. and Melancon, S. and Rupar, T. and Clarke, L.A.
DOI: 10.1016/j.ymgme.2008.05.001
2008

Characterization of Fabry Disease in 352 Pediatric Patients in the Fabry Registry
Pediatric Research
Hopkin, R.J. and Bissler, J. and Banikazemi, M. and Clarke, L. and Eng, C.M. and Germain, D.P. and Lemay, R. and Tylki-Szymanska, A. and Wilcox, W.R.
DOI: 10.1203/PDR.0b013e318183f132
2008

Pharmacokinetics of sapropterin in patients with phenylketonuria
Clinical Pharmacokinetics
Feillet, F. and Clarke, L. and Meli, C. and Lipson, M. and Morris, A.A. and Harmatz, P. and Mould, D.R. and Green, B. and Dorenbaum, A. and Giovannini, M. and Foehr, E.
DOI: 10.2165/0003088-200847120-00006
2008

Idursulfase for the treatment of mucopolvsaccharidosis II
Expert Opinion on Pharmacotherapy
Clarke, L.A.
DOI: 10.1517/14656566.9.2.311
2008

Generation of a conditional knockout of murine glucocerebrosidase: Utility for the study of Gaucher disease
Molecular Genetics and Metabolism
Sinclair, G.B. and Jevon, G. and Colobong, K.E. and Randall, D.R. and Choy, F.Y.M. and Clarke, L.A.
DOI: 10.1016/j.ymgme.2006.09.008
2007

Mucopolysaccharidosis I
Lysosomal Storage Disorders
Clarke, L.A.
DOI: 10.1007/978-0-387-70909-3_24
2007

Mucopolysaccharidosis II
Lysosomal Storage Disorders
Clarke, L.A.
DOI: 10.1007/978-0-387-70909-3_25
2007

A Phase III Extension Study of Aldurazyme®(Laronidase) in Mucopolysaccharidosis I
Clinical Therapeutics
Clarke, L.A. and Wraith, J.E. and Beck, M. and Kolodny, E.H. and Pastores, G.M. and Muenzer, J.
DOI: 10.1016/S0149-2918(07)80472-3
2007

A hemizygous SCO2 mutation in an early onset rapidly progressive, fatal cardiomyopathy
Molecular Genetics and Metabolism
Leary, S.C. and Mattman, A. and Wai, T. and Koehn, D.C. and Clarke, L.A. and Chan, S. and Lomax, B. and Eydoux, P. and Vallance, H.D. and Shoubridge, E.A.
DOI: 10.1016/j.ymgme.2006.04.016
2006

Cardiac functional and histopathologic findings in humans and mice with mucopolysaccharidosis type I: Implications for assessment of therapeutic interventions in Hurler syndrome
Pediatric Research
Braunlin, E. and Mackey-Bojack, S. and Panoskaltsis-Mortari, A. and Berry, J.M. and Mcelmurry, R.T. and Riddle, M. and Sun, L.-Y. and Clarke, L.A. and Tolar, J. and Blazar, B.R.
DOI: 10.1203/01.pdr.0000190579.24054.39
2006

Heparin cofactor II-thrombin complex in MPS I: A biomarker of MPS disease
Molecular Genetics and Metabolism
Randall, D.R. and Sinclair, G.B. and Colobong, K.E. and Hetty, E. and Clarke, L.A.
DOI: 10.1016/j.ymgme.2006.01.005
2006

Synthesis of enzymatically active human a-L-iduronidase in Arabidopsis cgl (complex glycan-deficient) seeds
Plant Biotechnology Journal
Downing, W.L. and Galpin, J.D. and Clemens, S. and Lauzon, S.M. and Samuels, A.L. and Pidkowich, M.S. and Clarke, L.A. and Kermode, A.R.
DOI: 10.1111/j.1467-7652.2005.00166.x
2006

Submicroscopic deletions and duplications in individuals with intellectual disability detected by Array-CGH
American Journal of Medical Genetics
Tyson, C. and Harvard, C. and Locker, R. and Friedman, J.M. and Langlois, S. and Lewis, M.E.S. and Van Allen, M. and Somerville, M. and Arbour, L. and Clarke, L. and McGilivray, B. and Yong, S.L. and Siegel-Bartel, J. and Rajcan-Separovic, E.
DOI: 10.1002/ajmg.a.31015
2005

A homology model for human a-L-iduronidase: Insights into human disease
Molecular Genetics and Metabolism
Rempel, B.P. and Clarke, L.A. and Withers, S.G.
DOI: 10.1016/j.ymgme.2004.12.006
2005

Spasms in children with definite and probable mitochondrial disease
European Journal of Neurology
Sadleir, L.G. and Connolly, M.B. and Applegarth, D. and Hendson, G. and Clarke, L. and Rakshi, C. and Farrell, K.
DOI: 10.1046/j.1351-5101.2003.00724.x
2004

Pseudo-lysosomal storage disease caused by EMLA cream
Journal of Inherited Metabolic Disease
Vallance, H. and Chaba, T. and Clarke, L. and Taylor, G.
DOI: 10.1023/B:BOLI.0000037352.98317.5a
2004

Enzyme replacement therapy for mucopolysaccharidosis I: A randomized, double-blinded, placebo-controlled, multinational study of recombinant human a-L-iduronidase (laronidase)
Journal of Pediatrics
Wraith, J.E. and Clarke, L.A. and Beck, M. and Kolodny, E.H. and Pastores, G.M. and Muenzer, J. and Rapoport, D.M. and Berger, K.I. and Swiedler, S.J. and Kakkis, E.D. and Braakman, T. and Chadbourne, E. and Walton-Bowen, K. and Cox, G.F.
DOI: 10.1016/j.jpeds.2004.01.046
2004

Long-Term Follow-Up of Three Individuals with Kabuki Syndrome
American Journal of Medical Genetics
Shalev, S.A. and Clarke, L.A. and Koehn, D. and Langlois, S. and Zackai, E.H. and Hall, J.G. and McDonald McGinn, D.M.
2004

Family 39 a-L-iduronidases and ß-D-xylosidases react through similar glycosyl-enzyme intermediates: Identification of the human iduronidase nucleophile
Biochemistry
Nieman, C.E. and Wong, A.W. and He, S. and Clarke, L. and Hopwood, J.J. and Withers, S.G.
DOI: 10.1021/bi034293v
2003

Sequence analysis of the mitochondrial genomes from Dutch pedigrees with leber hereditary optic neuropathy
American Journal of Human Genetics
Howell, N. and Oostra, R.-J. and Bolhuis, P.A. and Spruijt, L. and Clarke, L.A. and Mackey, D.A. and Preston, G. and Herrnstadt, C.
DOI: 10.1086/375537
2003

Mucopolysaccharidosis type VII (Sly syndrome) presenting as neonatal cholestasis with hepatosplenomegaly
Journal of Pediatric Gastroenterology and Nutrition
Gillett, P.M. and Schreiber, R.A. and Jevon, G.P. and Israel, D.M. and Warshawski, T. and Vallance, H. and Clarke, L.A.
DOI: 10.1097/00005176-200108000-00025
2001

Recombinant proteins for genetic disease
Clinical Genetics
Russell, C.S. and Clarke, L.A.
DOI: 10.1034/j.1399-0004.1999.550601.x
1999

Murine MPS I: Insights into the pathogenesis of Hurler syndrome
Clinical Genetics
Russell, C. and Hendson, G. and Jevon, G. and Matlock, T. and Yu, J. and Aklujkar, M. and Ng, K.-Y. and Clarke, L.A.
1998

Murine mucopolysaccharidosis type I: Targeted disruption of the murine a-L-iduronidase gene
Human Molecular Genetics
Clarke, L.A. and Russell, C.S. and Pownall, S. and Warrington, C.L. and Borowski, A. and Dimmick, J.E. and Toone, J. and Jirik, F.R.
DOI: 10.1093/hmg/6.4.503
1997

A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome
American Journal of Human Genetics
Muenke, M., Gripp, K.W., McDonald-McGinn, D.M., Gaudenz, K., Whitaker, L.A., Bartlett, S.P., Markowitz, R.I., Robin, N.H., Nwokoro, N., Mulvihill, J.J., Losken, H.W., Mulliken, J.B., Guttmacher, A.E., Wilroy, R.S., Clarke, L.A., Hollway, G., Adès, L.C., Haan, E.A., Mulley, J.C., Cohen Jr., M.M., Bellus, G.A., Francomano, C.A., Moloney, D.M., Wall, S.A., Wilkie, A.O.M., Zackai, E.H.
1997

Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes
Nature Genetics
Bellus, G.A. and Gaudenz, K. and Zackai, E.H. and Clarke, L.A. and Szabo, J. and Francomano, C.A. and Muenke, M.
DOI: 10.1038/ng1096-174
1996

Isolated mitochondria from frozen muscle have limited value in diagnostics
European Journal of Pediatrics
Scholte, H.R. and Trijbels, J.M.F. and Applegarth, D.A. and Tong, T. and Clarke, L.A.
DOI: 10.1007/BF01972981
1995

Molecular genetics of muccpolysaccharidosis type I: Diagnostic, clinical, and biological implications
Human Mutation
Scott, H.S. and Bunge, S. and Gal, A. and Clarke, L.A. and Morris, C.P. and Hopwood, J.J.
DOI: 10.1002/humu.1380060403
1995

Stability of frozen muscle used for mitochondrial enzyme assays
European Journal of Pediatrics
Applegarth, D.A. and Tong, T. and Clarke, L.A.
DOI: 10.1007/BF01959232
1994

Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm
Nature Genetics
Telenius, H. and Kremer, B. and Goldberg, Y.P. and Theilmann, J. and Andrew, S.E. and Zeisler, J. and Adam, S. and Greenberg, C. and Ives, E.J. and Clarke, L.A. and Hayden, M.R.
DOI: 10.1038/ng0494-409
1994

Erratum: Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm (Nature Genetics (1994) 6 (409-413))
Nature Genetics
Telenius, H. and Kremer, B. and Goldberg, Y.P. and Theilmann, J. and Andrew, S.E. and Zeisler, J. and Adam, S. and Greenberg, C. and Ives, E.J. and Clarke, L.A. and Hayden, M.R.
1994

Analysis of DNA changes in the LPL gene in patients with familial combined hyperlipidemia
Arteriosclerosis, Thrombosis, and Vascular Biology
Gagné, E., Genest Jr., J., Zhang, H., Clarke, L.A., Hayden, M.R.
1994

Mutation analysis of 19 North American mucopolysaccharidosis type I patients: Identification of two additional frequent mutations
Human Mutation
Clarke, L.A. and Nelson, P.V. and Warrington, C.L. and Morris, C.P. and Hopwood, J.J. and Scott, H.S.
DOI: 10.1002/humu.1380030316
1994

Tetrasomy 12p (Pallister-Killian syndrome): Ultrasound indicators and confirmation by interphase fish
Prenatal Diagnosis
Wilson, R.D. and Harrison, K. and Clarke, L.A. and Yong, S.L.
DOI: 10.1002/pd.1970140904
1994

Murine a-l-Iduronidase: cDNA Isolation and Expression
Genomics
Clarke, L.A. and Nasir, J. and Zhang, H. and McDonald, H. and Applegarth, D.A. and Hayden, M.R. and Toone, J.
DOI: 10.1006/geno.1994.1621
1994

Reports: Linkage of pfeiffer syndrome to chromosome 8 centromere and evidence for genetic heterogeneity
Human Molecular Genetics
Robin, N.H. and Feldman, G.J. and Mitchell, H.F. and Lorenz, P. and Wilroy, R.S. and Zackal, E.H. and Aiianson, J.E. and Reich, E.W. and Pfeiffer, R.A. and Clarke, L.A. and Warmani, M.L. and Mulliken, J.B. and Brueton, L.A. and Winter, R.M. and Price, R.A. and Gasser, D.L. and Muenke, M.
DOI: 10.1093/hmg/3.12.2153
1994

A PCR method for accurate assessment of trinucleotide repeat expansion in huntington disease
Human Molecular Genetics
Goldberg, Y.P. and Andrew, S.E. and Clarke, L.A. and Hayden, M.R.
DOI: 10.1093/hmg/2.6.635
1993

Long term survival of an infant with sirenomelia
American Journal of Medical Genetics
Clarke, L.A. and Stringer, D.A. and Fraser, G.C. and Siu Li Yong
DOI: 10.1002/ajmg.1320450303
1993

Identification of an Alu retrotransposition event in close proximity to a strong candidate gene for Huntington's disease
Nature
Goldberg, Y.P. and Rommens, J.M. and Andrew, S.E. and Hutchinson, G.B. and Lin, B. and Theilmann, J. and Graham, R. and Glaves, M.L. and Starr, E. and McDonald, H. and Nasir, J. and Schappert, K. and Kalchman, M.A. and Clarke, L.A. and Hayden, M.R.
1993

Erratum: A transcription map of the region containing the Huntington disease gene (Human molecular genetics (1993) 2 (901-907))
Human Molecular Genetics
Rommens, J.M. and Lin, B. and Hutchinson, G.B. and Andrew, S.E. and Goldberg, Y.P. and Glaves, M.L. and Graham, R. and Lai, V. and McArthur, J. and Nasir, J. and Theilmann, J. and McDonald, H. and Kalchman, M. and Clarke, L.A. and Schappert, K. and Hayden, M.R.
1993

Two novel mutations causing mucopolysaccharidosis type i detected by single strand conformational analysis of the a-L-iduronidase gene
Human Molecular Genetics
Clarke, L.A. and Scott, H.S.
DOI: 10.1093/hmg/2.8.1311
1993

A transcription map of the region containing the huntington disease gene
Human Molecular Genetics
Rommens, J.M. and Lin, B. and Hutchinson, G.B. and Andrew, S.E. and Goldberg, Y.P. and Glaves, M.L. and Graham, R. and Lal, V. and Mcarthur, J. and Nasir, J. and Theilmann, J. and Mcdonald, H. and Kalchman, M. and Clarke, L.A. and Schappert, K. and Hayden, M.R.
DOI: 10.1093/hmg/2.7.901
1993

Cloning and mapping of the a-adducin gene close to D4S95 and assessment of its relationship to huntington disease
Human Molecular Genetics
Goldberg, Y.P. and Lin, B.-Y. and Andrew, S.E. and Nasir, J. and Graham, R. and Glaves, M.L. and Hutchinson, G. and Theilmann, J. and Ginzinger, D.G. and Schappert, K. and Clarke, L. and Rommens, J.M. and Hayden, M.R.
DOI: 10.1093/hmg/1.9.669
1992

Nonsense-codon mutations of the ornithine aminotransferase gene with decreased levels of mutant mRNA in gyrate atrophy
American Journal of Human Genetics
Mashima, Y. and Murakami, A. and Weleber, R.G. and Kennaway, N.G. and Clarke, L. and Shiono, T. and Inana, G.
1992

Mitochondrial disorders in pediatrics: Clinical, biochemical, and genetic implications
Pediatric Clinics of North America
Clarke, L.A.
1992

A mutation in the human lipoprotein lipase gene as the most common cause of familial chylomicronemia in French Canadians
New England Journal of Medicine
Ma, Y., Henderson, H.E., Ven Murthy, M.R., Roederer, G., Monsalve, M.V., Clarke, L.A., Normand, T., Julien, P., Gagné, C., Lambert, M., Davignon, J., Lupien, P.J., Brunzell, J., Hayden, M.R.
1991

Sudden, unexpected, natural death in childhood
Fetal and Pediatric Pathology
Norman, M.G. and Taylor, G.P. and Clarke, L.A.
DOI: 10.3109/15513819009064711
1990

Crystal diaper syndrome.
CMAJ : Canadian Medical Association journal = journal de l"Association medicale canadienne
Clarke, L.A. and Applegarth, D.A.
1989

Research

Clinical trial of BH4 for the treatment of classical PKU
It has now been suggested that small molecules can act as chemical chaperones for misfolded proteins that are caused by point mutations of genes. PKU is an inborn error of metabolism that is currently treated by very restrictive diet. In vitro studies have shown that BH4 can stabilize mutant PAH enzyme and lead to greater tolerance of PHE in the diet.

Proteomic approach to the identification of biomarkers of MPS disease
This project involves the identification, through serum proteomic studies, markers of disease severity and responsiveness. Markers will initially be identified in a murine model and subsequently validated in human samples.

Clinical trial of recombinant iduronidase in the treatment of MPSI
Clinical trial of recombinant iduronidase in the treatment of MPSI. This is a complex multicenter multinational clinical trial of the use of iduronidase for the treatment of the genetic disease MPS I.

Honours & Awards

Canadian Glyconomics network Award- 2017

Canadian Organization for Rare Disorders (CORD) Rarity Award for Scientific Excellence - 2013.

Research Group Members

Anita Thomas, Research Assistant / Research Technician
Steven Zhou