- 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
-
Somatic mosaicism detected by genome-wide sequencing in 500 parent–child trios with suspected genetic disease: clinical and genetic counseling implications
Molecular Case Studies
Courtney B. Cook and Linlea Armstrong and Cornelius F. Boerkoel and Lorne A. Clarke and Christèle du Souich and Michelle K. Demos and William T. Gibson and Harinder Gill and Elena Lopez and Millan S. Patel and Kathryn Selby and Ziad Abu-Sharar and Alison M. Elliott and Jan M. Friedman
DOI: 10.1101/mcs.a006125
12/2021Newborn Screening for Mucopolysaccharidosis I: Moving Forward Learning from Experience
International Journal of Neonatal Screening
Lorne A. Clarke and Patricia Dickson and N. Matthew Ellinwood and Terri L. Klein
DOI: 10.3390/ijns6040091
11/2020Genotype-phenotype relationships in mucopolysaccharidosis type I (MPS I): Insights from the International MPS I Registry
Clinical Genetics
Lorne A. Clarke and Roberto Giugliani and Nathalie Guffon and Simon A. Jones and Hillary A. Keenan and Maria V. Munoz-Rojas and Torayuki Okuyama and David Viskochil and Chester B. Whitley and Frits A. Wijburg and Joseph Muenzer
DOI: 10.1111/cge.13583
10/2019RAPIDOMICS: rapid genome-wide sequencing in a neonatal intensive care unit—successes and challenges
European Journal of Pediatrics
DOI: 10.1007/s00431-019-03399-4
06/2019Low-dose agalsidase beta treatment in male pediatric patients with Fabry disease: A 5-year randomized controlled trial
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2019.03.010
05/2019Mucopolysaccharidosis Type I Newborn Screening: Best Practices for Diagnosis and Management
Journal of Pediatrics
DOI: 10.1016/j.jpeds.2016.11.036
2016Implementing evidence-driven individualized treatment plans within Morquio A Syndrome
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2015.12.157
2016Is it Fabry disease?
Genetics in Medicine
DOI: 10.1038/gim.2016.55
201612year follow up of enzyme-replacement therapy in two siblings with attenuated mucopolysaccharidosis I: The important role of early treatment
BMC Medical Genetics
DOI: 10.1186/s12881-016-0284-4
2016The clinical spectrum and pathophysiology of skeletal complications in lysosomal storage disorders
Best Practice and Research: Clinical Endocrinology and Metabolism
DOI: 10.1016/j.beem.2014.08.010
2015Characterization of early disease status in treatment-naive male paediatric patients with fabry disease enrolled in a randomized clinical trial
PLoS ONE
DOI: 10.1371/journal.pone.0124987
2015Extracellular matrix disruption is an early event in the pathogenesis of skeletal disease in mucopolysaccharidosis I
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2014.09.012
2015Mucopolysaccharidosis IVA (Morquio A syndrome) and VI (Maroteaux-Lamy syndrome): Under-recognized and challenging to diagnose
Skeletal Radiology
DOI: 10.1007/s00256-013-1797-y
2014Transgenic mice expressing human glucocerebrosidase variants: Utility for the study of Gaucher disease
Blood Cells, Molecules, and Diseases
DOI: 10.1016/j.bcmd.2013.03.006
2013Fetal progeria: Prenatal sonographic findings in petty syndrome
Journal of Ultrasound in Medicine
DOI: 10.7863/ultra.32.5.881
2013Biomarkers
Advances in Gaucher Disease: Basic and Clinical Perspectives
DOI: 10.2217/EBO.12.189
2013Capturing phenotypic heterogeneity in MPS I: Results of an international consensus procedure
Orphanet Journal of Rare Diseases
DOI: 10.1186/1750-1172-7-22
2012The role of enzyme replacement therapy in severe Hunter syndrome-an expert panel consensus
European Journal of Pediatrics
DOI: 10.1007/s00431-011-1606-3
2012Longitudinal observations of serum heparin cofactor II-thrombin complex in treated Mucopolysaccharidosis i and II patients
Journal of Inherited Metabolic Disease
DOI: 10.1007/s10545-011-9369-6
2012Biomarkers for the mucopolysaccharidoses: Discovery and clinical utility
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2012.05.003
2012Production of a-L-iduronidase in maize for the potential treatment of a human lysosomal storage disease
Nature Communications
DOI: 10.1038/ncomms2070
2012Production of active human glucocerebrosidase in seeds of Arabidopsis thaliana complex-glycan-deficient (cgl) plants
Glycobiology
DOI: 10.1093/glycob/cwr157
2012Left ventricular aneurysm in an adult patient with mucopolysaccharidosis type I: Comment on pathogenesis of a novel complication
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2012.06.001
2012Pathogenesis of skeletal and connective tissue involvement in the mucopolysaccharidoses: Glycosaminoglycan storage is merely the instigator
Rheumatology
DOI: 10.1093/rheumatology/ker395
2011Exome sequencing identifies SMAD3 mutations as a cause of familial thoracic aortic aneurysm and dissection with intracranial and other arterial aneurysms
Circulation Research
DOI: 10.1161/CIRCRESAHA.111.248161
2011Characterization of an MPS I-H knock-in mouse that carries a nonsense mutation analogous to the human IDUA-W402X mutation
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2009.08.002
2010Corrigendum 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
DOI: 10.1016/j.ymgme.2009.12.013
2010Enzyme-replacement therapy in a 5-month-old boy with attenuated presymptomatic MPS I: 5-year follow-up
Pediatrics
DOI: 10.1542/peds.2009-1728
2010Imaging of enzyme replacement therapy using PET
Proceedings of the National Academy of Sciences of the United States of America
DOI: 10.1073/pnas.1003247107
2010Urolithiasis and hepatotoxicity are linked to the anion transporter Sat1 in mice
Journal of Clinical Investigation
DOI: 10.1172/JCI31474
2010Mucopolysaccharidosis I: Management and treatment guidelines
Pediatrics
DOI: 10.1542/peds.2008-0416
2009Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I
Pediatrics
DOI: 10.1542/peds.2007-3847
2009The mucopolysaccharidoses: A success of molecular medicine (Expert Reviews in Molecular Medicine (2008) 10, (e1) DOI: 10.1017/S1462399408000550)
Expert Reviews in Molecular Medicine
DOI: 10.1017/S1462399409001185
2009Production and characterization of soluble human lysosomal enzyme a-iduronidase with high activity from culture media of transgenic tobacco BY-2 cells
Plant Science
DOI: 10.1016/j.plantsci.2009.08.016
2009Intracranial calcification after cord blood neonatal transplantation for Krabbe disease
Neuropediatrics
DOI: 10.1055/s-0029-1243189
2009Glycosaminoglycan-mediated loss of cathepsin K collagenolytic activity in MPS I contributes to osteoclast and growth plate abnormalities
American Journal of Pathology
DOI: 10.2353/ajpath.2009.090211
2009Pharmacokinetics of sapropterin in patients with phenylketonuria
Clinical Pharmacokinetics
DOI: 10.2165/0003088-200847120-00006
2008Characterization of Fabry Disease in 352 Pediatric Patients in the Fabry Registry
Pediatric Research
DOI: 10.1203/PDR.0b013e318183f132
2008Heparin cofactor II-thrombin complex: A biomarker of MPS disease
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2008.05.001
2008The mucopolysaccharidoses: A success of molecular medicine
Expert Reviews in Molecular Medicine
DOI: 10.1017/S1462399408000550
2008Idursulfase for the treatment of mucopolvsaccharidosis II
Expert Opinion on Pharmacotherapy
DOI: 10.1517/14656566.9.2.311
2008Generation of a conditional knockout of murine glucocerebrosidase: Utility for the study of Gaucher disease
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2006.09.008
2007A Phase III Extension Study of Aldurazyme®(Laronidase) in Mucopolysaccharidosis I
Clinical Therapeutics
DOI: 10.1016/S0149-2918(07)80472-3
2007Mucopolysaccharidosis II
Lysosomal Storage Disorders
DOI: 10.1007/978-0-387-70909-3_25
2007Mucopolysaccharidosis I
Lysosomal Storage Disorders
DOI: 10.1007/978-0-387-70909-3_24
2007Synthesis of enzymatically active human a-L-iduronidase in Arabidopsis cgl (complex glycan-deficient) seeds
Plant Biotechnology Journal
DOI: 10.1111/j.1467-7652.2005.00166.x
2006A hemizygous SCO2 mutation in an early onset rapidly progressive, fatal cardiomyopathy
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2006.04.016
2006Cardiac functional and histopathologic findings in humans and mice with mucopolysaccharidosis type I: Implications for assessment of therapeutic interventions in Hurler syndrome
Pediatric Research
DOI: 10.1203/01.pdr.0000190579.24054.39
2006Heparin cofactor II-thrombin complex in MPS I: A biomarker of MPS disease
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2006.01.005
2006Submicroscopic deletions and duplications in individuals with intellectual disability detected by Array-CGH
American Journal of Medical Genetics
DOI: 10.1002/ajmg.a.31015
2005A homology model for human a-L-iduronidase: Insights into human disease
Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2004.12.006
2005Long-Term Follow-Up of Three Individuals with Kabuki Syndrome
American Journal of Medical Genetics
2004Spasms in children with definite and probable mitochondrial disease
European Journal of Neurology
DOI: 10.1046/j.1351-5101.2003.00724.x
2004Pseudo-lysosomal storage disease caused by EMLA cream
Journal of Inherited Metabolic Disease
DOI: 10.1023/B:BOLI.0000037352.98317.5a
2004Enzyme replacement therapy for mucopolysaccharidosis I: A randomized, double-blinded, placebo-controlled, multinational study of recombinant human a-L-iduronidase (laronidase)
Journal of Pediatrics
DOI: 10.1016/j.jpeds.2004.01.046
2004Sequence analysis of the mitochondrial genomes from Dutch pedigrees with leber hereditary optic neuropathy
American Journal of Human Genetics
DOI: 10.1086/375537
2003Family 39 a-L-iduronidases and ß-D-xylosidases react through similar glycosyl-enzyme intermediates: Identification of the human iduronidase nucleophile
Biochemistry
DOI: 10.1021/bi034293v
2003Mucopolysaccharidosis type VII (Sly syndrome) presenting as neonatal cholestasis with hepatosplenomegaly
Journal of Pediatric Gastroenterology and Nutrition
DOI: 10.1097/00005176-200108000-00025
2001Recombinant proteins for genetic disease
Clinical Genetics
DOI: 10.1034/j.1399-0004.1999.550601.x
1999Murine MPS I: Insights into the pathogenesis of Hurler syndrome
Clinical Genetics
1998A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome
American Journal of Human Genetics
1997Murine mucopolysaccharidosis type I: Targeted disruption of the murine a-L-iduronidase gene
Human Molecular Genetics
DOI: 10.1093/hmg/6.4.503
1997Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes
Nature Genetics
DOI: 10.1038/ng1096-174
1996Isolated mitochondria from frozen muscle have limited value in diagnostics
European Journal of Pediatrics
DOI: 10.1007/BF01972981
1995Molecular genetics of muccpolysaccharidosis type I: Diagnostic, clinical, and biological implications
Human Mutation
DOI: 10.1002/humu.1380060403
1995Erratum: Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm (Nature Genetics (1994) 6 (409-413))
Nature Genetics
1994Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm
Nature Genetics
DOI: 10.1038/ng0494-409
1994Stability of frozen muscle used for mitochondrial enzyme assays
European Journal of Pediatrics
DOI: 10.1007/BF01959232
1994Tetrasomy 12p (Pallister-Killian syndrome): Ultrasound indicators and confirmation by interphase fish
Prenatal Diagnosis
DOI: 10.1002/pd.1970140904
1994Murine a-l-Iduronidase: cDNA Isolation and Expression
Genomics
DOI: 10.1006/geno.1994.1621
1994Reports: Linkage of pfeiffer syndrome to chromosome 8 centromere and evidence for genetic heterogeneity
Human Molecular Genetics
DOI: 10.1093/hmg/3.12.2153
1994Mutation analysis of 19 North American mucopolysaccharidosis type I patients: Identification of two additional frequent mutations
Human Mutation
DOI: 10.1002/humu.1380030316
1994Analysis of DNA changes in the LPL gene in patients with familial combined hyperlipidemia
Arteriosclerosis, Thrombosis, and Vascular Biology
1994Erratum: A transcription map of the region containing the Huntington disease gene (Human molecular genetics (1993) 2 (901-907))
Human Molecular Genetics
1993Two novel mutations causing mucopolysaccharidosis type i detected by single strand conformational analysis of the a-L-iduronidase gene
Human Molecular Genetics
DOI: 10.1093/hmg/2.8.1311
1993A PCR method for accurate assessment of trinucleotide repeat expansion in huntington disease
Human Molecular Genetics
DOI: 10.1093/hmg/2.6.635
1993A transcription map of the region containing the huntington disease gene
Human Molecular Genetics
DOI: 10.1093/hmg/2.7.901
1993Long term survival of an infant with sirenomelia
American Journal of Medical Genetics
DOI: 10.1002/ajmg.1320450303
1993Identification of an Alu retrotransposition event in close proximity to a strong candidate gene for Huntington's disease
Nature
1993Nonsense-codon mutations of the ornithine aminotransferase gene with decreased levels of mutant mRNA in gyrate atrophy
American Journal of Human Genetics
1992Cloning and mapping of the a-adducin gene close to D4S95 and assessment of its relationship to huntington disease
Human Molecular Genetics
DOI: 10.1093/hmg/1.9.669
1992Mitochondrial disorders in pediatrics: Clinical, biochemical, and genetic implications
Pediatric Clinics of North America
1992A mutation in the human lipoprotein lipase gene as the most common cause of familial chylomicronemia in French Canadians
New England Journal of Medicine
1991Sudden, unexpected, natural death in childhood
Fetal and Pediatric Pathology
DOI: 10.3109/15513819009064711
1990Crystal diaper syndrome.
CMAJ : Canadian Medical Association journal = journal de l"Association medicale canadienne
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 & AwardsCanadian Glyconomics network Award- 2017
Canadian Organization for Rare Disorders (CORD) Rarity Award for Scientific Excellence - 2013.
Students rave about Mini Med School BC
Of the nearly 150 Grade 10-12 students who attended Mini Med School BC - Vancouver Island, 100 per cent said they'd recommend the daylong health science youth outreach and public education program to others.
