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Genomes and Genes | C R ScriverSummaryAffiliation: McGill University Country: Canada Publications
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Publications
The PAH gene, phenylketonuria, and a paradigm shiftCharles R Scriver
Department of Human Genetics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada
Hum Mutat 28:831-45. 2007..Knowledge about PKU reveals genomic components of both disease and health...
2001 ASHG Award for Excellence in Education. ... And know the place for the first timeCharles R Scriver
Montreal Children's Hospital, Montreal, Quebec, Canada
Am J Hum Genet 70:317-23. 2002- Translating knowledge into practice in the "post-genome" eraC R Scriver
Department of Biology, McGill University, Montreal Children s Hospital, Montreal, Quebec, Canada
Acta Paediatr 93:294-300. 2004.... - After the genome--the phenome?C R Scriver
Department of Biology, McGill University, McGill University Health Center, A 721, Montreal Children s Hospital, 2300 Tupper Street, Montreal, Quebec, Canada H3H 1P3
J Inherit Metab Dis 27:305-17. 2004..Although the Word is common to all, most men live as if each had a private wisdom of his own.Herakleitos.. - Community genetics and dignity in diversity in the Quebec Network of Genetic MedicineCharles R Scriver
Department of Biology, Faculties of Science and Medicine, McGill University, Montreal, Canada
Community Genet 9:142-52. 2006..QNGM performed economic analyses of its major programs and followed prevailing ethical guidelines. Its global budget and integrated structure terminated in 1994, although some of its programs continue independently... - Henry Friesen Award Lecture. Work, the clinician-scientist and human biochemical geneticsC R Scriver
Department of Human Genetics, McGill University and McGill University Health Centre, Montreal, Que
Clin Invest Med 24:179-95. 2001..What can be known and what ought to be done, with knowledge about human genetics, to benefit individuals, families and communities (society), is both opportunity and challenge... - PAHdb 2003: what a locus-specific knowledgebase can doCharles R Scriver
Department of Human Genetics, McGill University Health Centre, Montreal, Canada
Hum Mutat 21:333-44. 2003..PAHdb contains data on the mouse gene (Pah) and on four orthologous mutant mouse models and their use (for example, in research on oral treatment of PKU with the enzyme phenylalanine ammonia lyase [EC 4.3.1.5])... - Does hereditary metabolic disease modulate senescence and ageing?C R Scriver
Department of Human Genetics, McGill University and McGill University Health Centre, Montreal, Quebec, Canada
J Inherit Metab Dis 25:235-51. 2002..reveal genetic factors? If there are 'ageing' mutations, of what types and with what effects? Will these initiatives lead to healthier longevity? A deeper question yet remains: why has human biology invested so greatly in grandparenthood?.. - Encomium to accompany "Of mice and children: reminiscences of a teratogeneticist"Charles R Scriver
McGill University, Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada
Am J Med Genet A 146:2177-8. 2008 - Why mutation analysis does not always predict clinical consequences: explanations in the era of genomicsCharles R Scriver
Department of Human Genetics, McGill University, , , Canada
J Pediatr 140:502-6. 2002 
Garrod's Croonian Lectures (1908) and the charter 'Inborn Errors of Metabolism': albinism, alkaptonuria, cystinuria, and pentosuria at age 100 in 2008Charles R Scriver
Department of Human Genetics, McGill University, Montreal, Canada
J Inherit Metab Dis 31:580-98. 2008....- Novel PKU mutation on haplotype 2 in French-CanadiansS W John
Department of Biology, McGill University, Montreal, Quebec
Am J Hum Genet 45:905-9. 1989..The mutations on haplotypes 1, 4, and 9 are not yet characterized. This preliminary study reveals a novel PKU mutation and considerable genetic heterogeneity at the phenylalanine hydroxylase locus in French-Canadians... - Recurrent mutation, gene conversion, or recombination at the human phenylalanine hydroxylase locus: evidence in French-Canadians and a catalog of mutationsS W John
McGill University Montreal Children s Hospital Research Institute, Department of Biology, Quebec, Canada
Am J Hum Genet 46:970-4. 1990..The finding is compatible with a recurrent mutation, gene conversion, or a single recombination between haplotypes 2 and 1. A tabulation of 20 known mutations at the PAH locus reveals three instances of putative recurrent mutation... - PAHdb: a locus-specific knowledgebaseC R Scriver
Departments of Biology, Human Genetics, Medicine, and Pediatrics, McGill University Health Centre, Montreal, Quebec, Canada
Hum Mutat 15:99-104. 2000..14.16.1); it is "patient friendly" in that it contains information for those personally involved with HPA/PKU (MIM# 261600). PAHdb also serves its community through direct interaction... - In vitro and in vivo correlations for I65T and M1V mutations at the phenylalanine hydroxylase locusS W John
Department of Pediatrics, McGill University Montreal Children s Hospital Research Institute, Quebec, Canada
Hum Mutat 1:147-53. 1992..Homozygosity for M1V and codominant inheritance of I65T/R408W were both associated with classical phenylketonuria... - Alterations in protein aggregation and degradation due to mild and severe missense mutations (A104D, R157N) in the human phenylalanine hydroxylase gene (PAH)P J Waters
De Belle Laboratory for Biochemical Genetics, McGill University Montreal Children s Hospital Research Institute, Quebec, Canada
Hum Mutat 12:344-54. 1998..Pulse-chase experiments showed increased PAH degradation, probably related to observed aberrations in protein folding and altered oligomerization, as a basic mechanism underlying effects of these missense mutations... - Homomeric and heteromeric interactions between wild-type and mutant phenylalanine hydroxylase subunits: evaluation of two-hybrid approaches for functional analysis of mutations causing hyperphenylalaninemiaP J Waters
DeBelle Laboratory for Biochemical Genetics, Montreal Children s Hospital, Quebec, Canada
Mol Genet Metab 73:230-8. 2001..These data provide a basis for functional studies on HPA-associated mutations affecting these enzymes... - Effect of gene dose and parental origin on bone histomorphometry in X-linked Hyp miceZ Q Qiu
Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada
Bone 34:134-9. 2004.... - A heteroallelic mutant mouse model: A new orthologue for human hyperphenylalaninemiaC N Sarkissian
Department of Biology, Department of Human Genetics, Department of Paediatrics, McGill University and Debelle Laboratory, McGill University Montreal Children s Hospital Research Institute, 2300 Tupper Street, A 717, Montreal, Quebec, Canada
Mol Genet Metab 69:188-94. 2000..The maternal HPA effect on the fetus correlates directly with the degree of hyperphenylalaninemia, but only the ENU2 strain has impaired learning... - Guidelines and recommendations for content, structure, and deployment of mutation databasesC R Scriver
DeBelle Laboratory, McGill University, Montreal Children s Hospital Research Institute, QC, Canada
Hum Mutat 13:344-50. 1999..A set of eight Recommendations completes these Guidelines for Content, Design, and Deployment of Mutation Databases... - Prediction of multiple hypermutable codons in the human PAH gene: codon 280 contains recurrent mutations in Quebec and other populationsS Byck
McGill University Montreal Children s Hospital Research Institute, Quebec, Canada
Hum Mutat 9:316-21. 1997..The PAH mutation database shows that the allele accounts for 1.5% of PKU chromosomes worldwide... - 3-Methylglutaconic aciduria: a marker for as yet unspecified disorders and the relevance of prenatal diagnosis in a 'new' type ('type 4')D Chitayat
De Belle Laboratory for Biochemical Genetics, Montreal Children s Hospital, Quebec, Canada
J Inherit Metab Dis 15:204-12. 1992..Postnatal follow-up confirmed absence of the disease. We give the normal values for amniotic fluid and results on these additional fetuses at risk (none affected)... - PAH Mutation Analysis Consortium Database: a database for disease-producing and other allelic variation at the human PAH locusL Hoang
The DeBelle Laboratory, McGill University Montreal Children s Hospital Research Institute, Montreal, Quebec, Canada
Nucleic Acids Res 24:127-31. 1996..The database, as a record of human genetic diversity, at a particular locus, contributes to the study of human evolution and demic expansion; it also has medical relevance... - Garrod's foresight; our hindsightC R Scriver
Department of Human Genetics, McGill University and McGill University Health Centre, Montreal, Quebec, Canada
J Inherit Metab Dis 24:93-116. 2001..What can be known and what ought to be done with knowledge about human genetics to benefit individuals, families and communities (society) is both opportunity and challenge... - The PAH mutation analysis consortium database: update 1996P Nowacki
The DeBelle Laboratory, McGill University Montreal Children s Hospital Research Institute, 2300 Tupper Street, Montreal, Quebec H3H 1P3, Canada
Nucleic Acids Res 25:139-42. 1997..The primary 'electronic publication' reports now vastly exceed print reports. PAHdb serves as a prototype for obtaining, storing and distributing records of human genetic variation... - Monogenic traits are not simple: lessons from phenylketonuriaC R Scriver
DeBelle Laboratory for Biochemical Genetics, Montreal Children s Hospital, 2300 Tupper Street, Montreal, Quebec, Canada H3H 1P3
Trends Genet 15:267-72. 1999.... - In vitro expression analysis of mutations in phenylalanine hydroxylase: linking genotype to phenotype and structure to functionP J Waters
Department of Pediatrics, McGill University, Montreal, Quebec, Canada
Hum Mutat 11:4-17. 1998..Data on in vitro expression of 35 inherited human mutations and 22 created rat mutations are reviewed here. The core data are accessible at the PAH Mutation Analysis Consortium Web site (http://www.mcgill.ca/pahdb)... - What we know that could influence future treatment of phenylketonuriaC N Sarkissian
Department of Biology, Human Genetics and Pediatrics, McGill University, Quebec, Canada
J Inherit Metab Dis 32:3-9. 2009..This knowledge is now being applied in the development of patient-specific therapies... - Parental origin of mutant allele does not explain absence of gene dose in X-linked Hyp miceZ Q Qiu
Department of Biology, McGill University, Montreal, Quebec, Canada
Genet Res 62:39-43. 1993..We found no effect on the distribution of trait values. We conclude that parental origin of mutant allele does not explain the absence of a gene dose effect in Hyp mice... - Human genetics: lessons from Quebec populationsC R Scriver
Departments of Human Genetics, Pediatrics, and Biology, McGill University, Montreal, Quebec, Canada
Annu Rev Genomics Hum Genet 2:69-101. 2001..How the population benefits from what is being learned about its structure and how its uniqueness could facilitate construction of a genomic map of linkage disequilibrium are discussed... - Hyperphenylalaninemia due to deficiency of 6-pyruvoyl tetrahydropterin synthase. Unusual gene dosage effect in heterozygotesC R Scriver
McGill University, Children s Hospital Research Institute, Montreal, Quebec, Canada
Hum Genet 77:168-71. 1987..The complex relationship between erythrocyte PTS activity, and biopterin synthesis in these families indicates genetic heterogeneity at the PTS locus... - A 25-year longitudinal analysis of treatment efficacy in inborn errors of metabolismPhilippe M Campeau
Division of Medical Genetics, Department of Pediatrics, A 608, Montreal Children s Hospital, McGill University Health Center, Montreal, Quebec, Canada
Mol Genet Metab 95:11-6. 2008.... - Hereditary tyrosinaemia type II in a consanguineous Ashkenazi Jewish family: intrafamilial variation in phenotype; absence of parental phenotype effects on the fetusD Chitayat
DeBelle Laboratory for Biochemical Genetics, Montreal Children s Hospital, Quebec, Canada
J Inherit Metab Dis 15:198-203. 1992..Maternal hypertyrosinaemia and maternal hyperphenylalaninaemia evidently constitute different risk factors for the fetus. Paternal hypertyrosinaemia is apparently not a risk to male infertility... - Audiometric evidence for two forms of X-linked hypophosphatemia in humans, apparent counterparts of Hyp and Gy mutations in mouseA Boneh
Department of Pediatrics, Montreal Children s Hospital, Quebec
Am J Med Genet 27:997-1003. 1987..We suggest the disease in these persons may be the human counterpart of the Gy phenotype in the mouse, which implies there are 2 forms of X-linked hypophosphatemia in humans... - A Pst+ polymorphism in the HEXA gene with an unusual geographic distributionF Kaplan
Department of Biochemical Genetics, McGill University, Montreal Children's Hospital Research Institute, Quebec, Canada
Eur J Hum Genet 1:301-5. 1993..In both cases the variant occurs on a chromosome carrying a novel TSD mutation (G772C) association with the B1 phenotype. The Pst+ G772C chromosomes are of Scots-Irish descent... - Five mutations at the PAH locus account for almost 90% of PKU mutations in French-Canadians from eastern QuebecS W John
MRC Group in Genetics, McGill University-Montreal Children's Hospital Research Institute, , Canada
Hum Mutat 1:72-4. 1992 - Prolidase deficiency: biochemical classification of allelesA P Boright
Department of Biology, McGill University, Montreal, Quebec, Canada
Am J Hum Genet 44:731-40. 1989..Allelic heterogeneity at the major locus and the amount of alternative peptidase activity encoded elsewhere appear to be determinants of the associated and heterogeneous clinical phenotype... - X-linked hypophosphataemia: a homologous phenotype in humans and mice with unusual organ-specific gene dosageC R Scriver
Department of Biology, McGill University, Montreal, Quebec, Canada
J Inherit Metab Dis 15:610-24. 1992.... - Guidelines and recommendations for content, structure, and deployment of mutation databases: II. Journey in progressC R Scriver
DeBelle Laboratory, McGill University Montreal Children s Hospital Research Institute, Montreal, Canada
Hum Mutat 15:13-5. 2000..The participating community (developers and users) have been moving the project along rapidly, as described here... - The human genome project will not replace the physicianCharles R Scriver
McGill University, , , Canada
CMAJ 171:1461-4. 2004 - Novel Tay-Sachs disease mutations from ChinaN Akalin
McGill University Montreal Children s Hospital Research Institute, Quebec, Canada
Hum Mutat 1:40-6. 1992..This mutation occurs at a CpG dinucleotide. It has been reported in an Italian TSD proband and causes defective intracellular transport of the alpha-subunit from the rough endoplasmic reticulum to the Golgi apparatus... - Preclinical evaluation of multiple species of PEGylated recombinant phenylalanine ammonia lyase for the treatment of phenylketonuriaChristineh N Sarkissian
Department of Biology, McGill University, Montreal, QC, Canada H3A 1B1
Proc Natl Acad Sci U S A 105:20894-9. 2008..Phenylalanine reduction occurred in a dose- and loading-dependent manner, and PEGylation reduced the neutralizing immune response to the enzyme. Human clinical trials with PEG-Av-p.C503S/p.C565S-PAL as a treatment for PKU are underway... 
FINDbase: a relational database recording frequencies of genetic defects leading to inherited disorders worldwideSjozef van Baal
Erasmus MC, MGC Department of Cell Biology and Genetics, Rotterdam, The Netherlands
Nucleic Acids Res 35:D690-5. 2007....- Structure-based chemical modification strategy for enzyme replacement treatment of phenylketonuriaLin Wang
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Mol Genet Metab 86:134-40. 2005..The three-dimensional structure of PAL provides a basis for understanding the properties of pegylated forms of PAL and strategies for structure-based re-engineering of PAL for PKU treatment... - Genetic diversity within the R408W phenylketonuria mutation lineages in EuropeOrna Tighe
Department of Pathology and National Centre for Newborn Screening, The Children s University Hospital, Dublin, Ireland
Hum Mutat 21:387-93. 2003..However, in the absence of a more extensive STR data-set, no such conclusions are possible for the respective R408W mutant lineages... - New approaches to treat PKU: how far are we?Nenad Blau
Department of Pediatrics, University of Zurich, Switzerland
Mol Genet Metab 81:1-2. 2004 - The last day of the past is the first day of the future: Transitional care for genetic patientsCharles R Scriver
Am J Med 117:615-7. 2004 - Correction of kinetic and stability defects by tetrahydrobiopterin in phenylketonuria patients with certain phenylalanine hydroxylase mutationsHeidi Erlandsen
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 101:16903-8. 2004..Of fundamental importance is the observation that BH4 appears to increase Phe catabolism if at least one of the two heterozygous mutations has any residual activity remaining... - Structure-based epitope and PEGylation sites mapping of phenylalanine ammonia-lyase for enzyme substitution treatment of phenylketonuriaAlejandra Gamez
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Mol Genet Metab 91:325-34. 2007.... - Recommendations of the 2006 Human Variome Project meetingRichard G H Cotton
Genomic Disorders Research Centre, St Vincent s Hospital Melbourne, 35 Victoria Parade, Melbourne, Victoria 3065, Australia
Nat Genet 39:433-6. 2007..Here we summarize the background of the project, the meeting and its recommendations... - Development of pegylated forms of recombinant Rhodosporidium toruloides phenylalanine ammonia-lyase for the treatment of classical phenylketonuriaAlejandra Gamez
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Mol Ther 11:986-9. 2005..The linear 20-kDa PEG-PAL combination abolished in vivo immunogenicity after repeated challenge while retaining full catabolic activity against phenylalanine, suggesting potential as a novel PKU therapeutic...