Identification and Characterization of an Inborn Error of Metabolism Caused by Dihydrofolate Reductase Deficiency
Identifieur interne : 000942 ( Pmc/Checkpoint ); précédent : 000941; suivant : 000943Identification and Characterization of an Inborn Error of Metabolism Caused by Dihydrofolate Reductase Deficiency
Auteurs : Siddharth Banka [Royaume-Uni] ; Henk J. Blom [Pays-Bas] ; John Walter [Royaume-Uni] ; Majid Aziz [Royaume-Uni] ; Jill Urquhart [Royaume-Uni] ; Christopher M. Clouthier [Canada] ; Gillian I. Rice [Royaume-Uni] ; Arjan P. M. De Brouwer [Pays-Bas] ; Emma Hilton [Royaume-Uni] ; Grace Vassallo [Royaume-Uni] ; Andrew Will [Royaume-Uni] ; Desirée E. C. Smith [Pays-Bas] ; Yvo M. Smulders [Pays-Bas] ; Ron A. Wevers [Pays-Bas] ; Robert Steinfeld [Allemagne] ; Simon Heales [Royaume-Uni] ; Yanick J. Crow [Royaume-Uni] ; Joelle N. Pelletier [Canada] ; Simon Jones [Royaume-Uni] ; William G. Newman [Royaume-Uni]Source :
- American Journal of Human Genetics [ 0002-9297 ] ; 2011.
Abstract
Dihydrofolate reductase (DHFR) is a critical enzyme in folate metabolism and an important target of antineoplastic, antimicrobial, and antiinflammatory drugs. We describe three individuals from two families with a recessive inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency due to a germline missense mutation in
Url:
DOI: 10.1016/j.ajhg.2011.01.004
PubMed: 21310276
PubMed Central: 3035707
Affiliations:
- Allemagne, Canada, Pays-Bas, Royaume-Uni
- Angleterre, Basse-Saxe, Grand Manchester
- Göttingen, Manchester
- Université de Manchester
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Blom</name><affiliation wicri:level="1"><nlm:aff id="aff2">Metabolic Unit, Department of Clinical Chemistry, Institute for Cardiovascular Research, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Metabolic Unit, Department of Clinical Chemistry, Institute for Cardiovascular Research, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam</wicri:regionArea><wicri:noRegion>1081 HV Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Walter, John" sort="Walter, John" uniqKey="Walter J" first="John" last="Walter">John Walter</name><affiliation wicri:level="4"><nlm:aff id="aff1">Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL</wicri:regionArea><orgName type="university">Université de Manchester</orgName><placeName><settlement type="city">Manchester</settlement><region type="nation">Angleterre</region><region nuts="2" type="region">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="Aziz, Majid" sort="Aziz, Majid" uniqKey="Aziz M" first="Majid" last="Aziz">Majid Aziz</name><affiliation wicri:level="1"><nlm:aff id="aff3">Paediatric Neurology, MAHSC, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Paediatric Neurology, MAHSC, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL</wicri:regionArea><wicri:noRegion>Manchester M13 9WL</wicri:noRegion></affiliation></author><author><name sortKey="Urquhart, Jill" sort="Urquhart, Jill" uniqKey="Urquhart J" first="Jill" last="Urquhart">Jill Urquhart</name><affiliation wicri:level="4"><nlm:aff id="aff1">Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL</wicri:regionArea><orgName type="university">Université de Manchester</orgName><placeName><settlement type="city">Manchester</settlement><region type="nation">Angleterre</region><region nuts="2" type="region">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="Clouthier, Christopher M" sort="Clouthier, Christopher M" uniqKey="Clouthier C" first="Christopher M." last="Clouthier">Christopher M. Clouthier</name><affiliation wicri:level="1"><nlm:aff id="aff4">Département de Biochimie and Département de Chimie, Université de Montréal, Montréal, Québec H3C 3J7, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Département de Biochimie and Département de Chimie, Université de Montréal, Montréal, Québec H3C 3J7</wicri:regionArea><wicri:noRegion>Québec H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Rice, Gillian I" sort="Rice, Gillian I" uniqKey="Rice G" first="Gillian I." last="Rice">Gillian I. Rice</name><affiliation wicri:level="4"><nlm:aff id="aff1">Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL</wicri:regionArea><orgName type="university">Université de Manchester</orgName><placeName><settlement type="city">Manchester</settlement><region type="nation">Angleterre</region><region nuts="2" type="region">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="De Brouwer, Arjan P M" sort="De Brouwer, Arjan P M" uniqKey="De Brouwer A" first="Arjan P. M." last="De Brouwer">Arjan P. M. De Brouwer</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Human Genetics, Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Human Genetics, Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre, Geert Grooteplein 10, 6525 GA Nijmegen</wicri:regionArea><wicri:noRegion>6525 GA Nijmegen</wicri:noRegion></affiliation></author><author><name sortKey="Hilton, Emma" sort="Hilton, Emma" uniqKey="Hilton E" first="Emma" last="Hilton">Emma Hilton</name><affiliation wicri:level="4"><nlm:aff id="aff1">Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL</wicri:regionArea><orgName type="university">Université de Manchester</orgName><placeName><settlement type="city">Manchester</settlement><region type="nation">Angleterre</region><region nuts="2" type="region">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="Vassallo, Grace" sort="Vassallo, Grace" uniqKey="Vassallo G" first="Grace" last="Vassallo">Grace Vassallo</name><affiliation wicri:level="1"><nlm:aff id="aff3">Paediatric Neurology, MAHSC, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Paediatric Neurology, MAHSC, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL</wicri:regionArea><wicri:noRegion>Manchester M13 9WL</wicri:noRegion></affiliation></author><author><name sortKey="Will, Andrew" sort="Will, Andrew" uniqKey="Will A" first="Andrew" last="Will">Andrew Will</name><affiliation wicri:level="1"><nlm:aff id="aff6">Paediatric Haematology, MAHSC, St. Mary's Hospital, Central Manchester Foundation NHS Trust, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Paediatric Haematology, MAHSC, St. Mary's Hospital, Central Manchester Foundation NHS Trust, Manchester M13 9WL</wicri:regionArea><wicri:noRegion>Manchester M13 9WL</wicri:noRegion></affiliation></author><author><name sortKey="Smith, Desiree E C" sort="Smith, Desiree E C" uniqKey="Smith D" first="Desirée E. C." last="Smith">Desirée E. C. Smith</name><affiliation wicri:level="1"><nlm:aff id="aff2">Metabolic Unit, Department of Clinical Chemistry, Institute for Cardiovascular Research, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Metabolic Unit, Department of Clinical Chemistry, Institute for Cardiovascular Research, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam</wicri:regionArea><wicri:noRegion>1081 HV Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Smulders, Yvo M" sort="Smulders, Yvo M" uniqKey="Smulders Y" first="Yvo M." last="Smulders">Yvo M. Smulders</name><affiliation wicri:level="1"><nlm:aff id="aff7">Department of Internal Medicine, Institute for Cardiovascular Research, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Internal Medicine, Institute for Cardiovascular Research, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam</wicri:regionArea><wicri:noRegion>1081 HV Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Wevers, Ron A" sort="Wevers, Ron A" uniqKey="Wevers R" first="Ron A." last="Wevers">Ron A. Wevers</name><affiliation wicri:level="1"><nlm:aff id="aff8">Laboratory of Genetic Endocrine and Metabolic Diseases, Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Laboratory of Genetic Endocrine and Metabolic Diseases, Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, Geert Grooteplein 10, 6525 GA Nijmegen</wicri:regionArea><wicri:noRegion>6525 GA Nijmegen</wicri:noRegion></affiliation></author><author><name sortKey="Steinfeld, Robert" sort="Steinfeld, Robert" uniqKey="Steinfeld R" first="Robert" last="Steinfeld">Robert Steinfeld</name><affiliation wicri:level="3"><nlm:aff id="aff9">Department of Pediatrics, University of Goettingen, Robert-Koch-Str. 40, D-37075 Goettingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatrics, University of Goettingen, Robert-Koch-Str. 40, D-37075 Goettingen</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Göttingen</settlement></placeName></affiliation></author><author><name sortKey="Heales, Simon" sort="Heales, Simon" uniqKey="Heales S" first="Simon" last="Heales">Simon Heales</name><affiliation wicri:level="1"><nlm:aff id="aff10">Neurometabolic Unit, National Hospital, Queen Square, Clinical and Molecular Genetics Unit, UCL Institute of Child Health & Enzyme and Metabolic Unit, Great Ormond Street Hospital, London WC1N 3JH, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Neurometabolic Unit, National Hospital, Queen Square, Clinical and Molecular Genetics Unit, UCL Institute of Child Health & Enzyme and Metabolic Unit, Great Ormond Street Hospital, London WC1N 3JH</wicri:regionArea><wicri:noRegion>London WC1N 3JH</wicri:noRegion></affiliation></author><author><name sortKey="Crow, Yanick J" sort="Crow, Yanick J" uniqKey="Crow Y" first="Yanick J." last="Crow">Yanick J. Crow</name><affiliation wicri:level="4"><nlm:aff id="aff1">Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL</wicri:regionArea><orgName type="university">Université de Manchester</orgName><placeName><settlement type="city">Manchester</settlement><region type="nation">Angleterre</region><region nuts="2" type="region">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="Pelletier, Joelle N" sort="Pelletier, Joelle N" uniqKey="Pelletier J" first="Joelle N." last="Pelletier">Joelle N. Pelletier</name><affiliation wicri:level="1"><nlm:aff id="aff4">Département de Biochimie and Département de Chimie, Université de Montréal, Montréal, Québec H3C 3J7, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Département de Biochimie and Département de Chimie, Université de Montréal, Montréal, Québec H3C 3J7</wicri:regionArea><wicri:noRegion>Québec H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Jones, Simon" sort="Jones, Simon" uniqKey="Jones S" first="Simon" last="Jones">Simon Jones</name><affiliation wicri:level="4"><nlm:aff id="aff1">Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL</wicri:regionArea><orgName type="university">Université de Manchester</orgName><placeName><settlement type="city">Manchester</settlement><region type="nation">Angleterre</region><region nuts="2" type="region">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="Newman, William G" sort="Newman, William G" uniqKey="Newman W" first="William G." last="Newman">William G. Newman</name><affiliation wicri:level="4"><nlm:aff id="aff1">Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL</wicri:regionArea><orgName type="university">Université de Manchester</orgName><placeName><settlement type="city">Manchester</settlement><region type="nation">Angleterre</region><region nuts="2" type="region">Grand Manchester</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21310276</idno><idno type="pmc">3035707</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035707</idno><idno type="RBID">PMC:3035707</idno><idno type="doi">10.1016/j.ajhg.2011.01.004</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">000352</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000352</idno><idno type="wicri:Area/Pmc/Curation">000352</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000352</idno><idno type="wicri:Area/Pmc/Checkpoint">000942</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000942</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Identification and Characterization of an Inborn Error of Metabolism Caused by Dihydrofolate Reductase Deficiency</title><author><name sortKey="Banka, Siddharth" sort="Banka, Siddharth" uniqKey="Banka S" first="Siddharth" last="Banka">Siddharth Banka</name><affiliation wicri:level="4"><nlm:aff id="aff1">Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL</wicri:regionArea><orgName type="university">Université de Manchester</orgName><placeName><settlement type="city">Manchester</settlement><region type="nation">Angleterre</region><region nuts="2" type="region">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="Blom, Henk J" sort="Blom, Henk J" uniqKey="Blom H" first="Henk J." last="Blom">Henk J. Blom</name><affiliation wicri:level="1"><nlm:aff id="aff2">Metabolic Unit, Department of Clinical Chemistry, Institute for Cardiovascular Research, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Metabolic Unit, Department of Clinical Chemistry, Institute for Cardiovascular Research, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam</wicri:regionArea><wicri:noRegion>1081 HV Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Walter, John" sort="Walter, John" uniqKey="Walter J" first="John" last="Walter">John Walter</name><affiliation wicri:level="4"><nlm:aff id="aff1">Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL</wicri:regionArea><orgName type="university">Université de Manchester</orgName><placeName><settlement type="city">Manchester</settlement><region type="nation">Angleterre</region><region nuts="2" type="region">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="Aziz, Majid" sort="Aziz, Majid" uniqKey="Aziz M" first="Majid" last="Aziz">Majid Aziz</name><affiliation wicri:level="1"><nlm:aff id="aff3">Paediatric Neurology, MAHSC, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Paediatric Neurology, MAHSC, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL</wicri:regionArea><wicri:noRegion>Manchester M13 9WL</wicri:noRegion></affiliation></author><author><name sortKey="Urquhart, Jill" sort="Urquhart, Jill" uniqKey="Urquhart J" first="Jill" last="Urquhart">Jill Urquhart</name><affiliation wicri:level="4"><nlm:aff id="aff1">Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL</wicri:regionArea><orgName type="university">Université de Manchester</orgName><placeName><settlement type="city">Manchester</settlement><region type="nation">Angleterre</region><region nuts="2" type="region">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="Clouthier, Christopher M" sort="Clouthier, Christopher M" uniqKey="Clouthier C" first="Christopher M." last="Clouthier">Christopher M. Clouthier</name><affiliation wicri:level="1"><nlm:aff id="aff4">Département de Biochimie and Département de Chimie, Université de Montréal, Montréal, Québec H3C 3J7, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Département de Biochimie and Département de Chimie, Université de Montréal, Montréal, Québec H3C 3J7</wicri:regionArea><wicri:noRegion>Québec H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Rice, Gillian I" sort="Rice, Gillian I" uniqKey="Rice G" first="Gillian I." last="Rice">Gillian I. Rice</name><affiliation wicri:level="4"><nlm:aff id="aff1">Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL</wicri:regionArea><orgName type="university">Université de Manchester</orgName><placeName><settlement type="city">Manchester</settlement><region type="nation">Angleterre</region><region nuts="2" type="region">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="De Brouwer, Arjan P M" sort="De Brouwer, Arjan P M" uniqKey="De Brouwer A" first="Arjan P. M." last="De Brouwer">Arjan P. M. De Brouwer</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Human Genetics, Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Human Genetics, Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre, Geert Grooteplein 10, 6525 GA Nijmegen</wicri:regionArea><wicri:noRegion>6525 GA Nijmegen</wicri:noRegion></affiliation></author><author><name sortKey="Hilton, Emma" sort="Hilton, Emma" uniqKey="Hilton E" first="Emma" last="Hilton">Emma Hilton</name><affiliation wicri:level="4"><nlm:aff id="aff1">Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL</wicri:regionArea><orgName type="university">Université de Manchester</orgName><placeName><settlement type="city">Manchester</settlement><region type="nation">Angleterre</region><region nuts="2" type="region">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="Vassallo, Grace" sort="Vassallo, Grace" uniqKey="Vassallo G" first="Grace" last="Vassallo">Grace Vassallo</name><affiliation wicri:level="1"><nlm:aff id="aff3">Paediatric Neurology, MAHSC, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Paediatric Neurology, MAHSC, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL</wicri:regionArea><wicri:noRegion>Manchester M13 9WL</wicri:noRegion></affiliation></author><author><name sortKey="Will, Andrew" sort="Will, Andrew" uniqKey="Will A" first="Andrew" last="Will">Andrew Will</name><affiliation wicri:level="1"><nlm:aff id="aff6">Paediatric Haematology, MAHSC, St. Mary's Hospital, Central Manchester Foundation NHS Trust, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Paediatric Haematology, MAHSC, St. Mary's Hospital, Central Manchester Foundation NHS Trust, Manchester M13 9WL</wicri:regionArea><wicri:noRegion>Manchester M13 9WL</wicri:noRegion></affiliation></author><author><name sortKey="Smith, Desiree E C" sort="Smith, Desiree E C" uniqKey="Smith D" first="Desirée E. C." last="Smith">Desirée E. C. Smith</name><affiliation wicri:level="1"><nlm:aff id="aff2">Metabolic Unit, Department of Clinical Chemistry, Institute for Cardiovascular Research, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Metabolic Unit, Department of Clinical Chemistry, Institute for Cardiovascular Research, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam</wicri:regionArea><wicri:noRegion>1081 HV Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Smulders, Yvo M" sort="Smulders, Yvo M" uniqKey="Smulders Y" first="Yvo M." last="Smulders">Yvo M. Smulders</name><affiliation wicri:level="1"><nlm:aff id="aff7">Department of Internal Medicine, Institute for Cardiovascular Research, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Internal Medicine, Institute for Cardiovascular Research, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam</wicri:regionArea><wicri:noRegion>1081 HV Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Wevers, Ron A" sort="Wevers, Ron A" uniqKey="Wevers R" first="Ron A." last="Wevers">Ron A. Wevers</name><affiliation wicri:level="1"><nlm:aff id="aff8">Laboratory of Genetic Endocrine and Metabolic Diseases, Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Laboratory of Genetic Endocrine and Metabolic Diseases, Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, Geert Grooteplein 10, 6525 GA Nijmegen</wicri:regionArea><wicri:noRegion>6525 GA Nijmegen</wicri:noRegion></affiliation></author><author><name sortKey="Steinfeld, Robert" sort="Steinfeld, Robert" uniqKey="Steinfeld R" first="Robert" last="Steinfeld">Robert Steinfeld</name><affiliation wicri:level="3"><nlm:aff id="aff9">Department of Pediatrics, University of Goettingen, Robert-Koch-Str. 40, D-37075 Goettingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatrics, University of Goettingen, Robert-Koch-Str. 40, D-37075 Goettingen</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Göttingen</settlement></placeName></affiliation></author><author><name sortKey="Heales, Simon" sort="Heales, Simon" uniqKey="Heales S" first="Simon" last="Heales">Simon Heales</name><affiliation wicri:level="1"><nlm:aff id="aff10">Neurometabolic Unit, National Hospital, Queen Square, Clinical and Molecular Genetics Unit, UCL Institute of Child Health & Enzyme and Metabolic Unit, Great Ormond Street Hospital, London WC1N 3JH, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Neurometabolic Unit, National Hospital, Queen Square, Clinical and Molecular Genetics Unit, UCL Institute of Child Health & Enzyme and Metabolic Unit, Great Ormond Street Hospital, London WC1N 3JH</wicri:regionArea><wicri:noRegion>London WC1N 3JH</wicri:noRegion></affiliation></author><author><name sortKey="Crow, Yanick J" sort="Crow, Yanick J" uniqKey="Crow Y" first="Yanick J." last="Crow">Yanick J. Crow</name><affiliation wicri:level="4"><nlm:aff id="aff1">Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL</wicri:regionArea><orgName type="university">Université de Manchester</orgName><placeName><settlement type="city">Manchester</settlement><region type="nation">Angleterre</region><region nuts="2" type="region">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="Pelletier, Joelle N" sort="Pelletier, Joelle N" uniqKey="Pelletier J" first="Joelle N." last="Pelletier">Joelle N. Pelletier</name><affiliation wicri:level="1"><nlm:aff id="aff4">Département de Biochimie and Département de Chimie, Université de Montréal, Montréal, Québec H3C 3J7, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Département de Biochimie and Département de Chimie, Université de Montréal, Montréal, Québec H3C 3J7</wicri:regionArea><wicri:noRegion>Québec H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Jones, Simon" sort="Jones, Simon" uniqKey="Jones S" first="Simon" last="Jones">Simon Jones</name><affiliation wicri:level="4"><nlm:aff id="aff1">Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL</wicri:regionArea><orgName type="university">Université de Manchester</orgName><placeName><settlement type="city">Manchester</settlement><region type="nation">Angleterre</region><region nuts="2" type="region">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="Newman, William G" sort="Newman, William G" uniqKey="Newman W" first="William G." last="Newman">William G. Newman</name><affiliation wicri:level="4"><nlm:aff id="aff1">Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL</wicri:regionArea><orgName type="university">Université de Manchester</orgName><placeName><settlement type="city">Manchester</settlement><region type="nation">Angleterre</region><region nuts="2" type="region">Grand Manchester</region></placeName></affiliation></author></analytic><series><title level="j">American Journal of Human Genetics</title><idno type="ISSN">0002-9297</idno><idno type="eISSN">1537-6605</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Dihydrofolate reductase (DHFR) is a critical enzyme in folate metabolism and an important target of antineoplastic, antimicrobial, and antiinflammatory drugs. We describe three individuals from two families with a recessive inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency due to a germline missense mutation in <italic>DHFR</italic>, resulting in profound enzyme deficiency. We show that cerebral folate levels, anemia, and pancytopenia of DHFR deficiency can be corrected by treatment with folinic acid. The characterization of this disorder provides evidence for the link between DHFR and metabolism of cerebral tetrahydrobiopterin, which is required for the formation of dopamine, serotonin, and norepinephrine and for the hydroxylation of aromatic amino acids. Moreover, this relationship provides insight into the role of folates in neurological conditions, including depression, Alzheimer disease, and Parkinson disease.</p></div></front></TEI><pmc article-type="brief-report"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Hum Genet</journal-id><journal-id journal-id-type="iso-abbrev">Am. J. Hum. Genet</journal-id><journal-title-group><journal-title>American Journal of Human Genetics</journal-title></journal-title-group><issn pub-type="ppub">0002-9297</issn><issn pub-type="epub">1537-6605</issn><publisher><publisher-name>Elsevier</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21310276</article-id><article-id pub-id-type="pmc">3035707</article-id><article-id pub-id-type="publisher-id">S0002-9297(11)00005-X</article-id><article-id pub-id-type="doi">10.1016/j.ajhg.2011.01.004</article-id><article-categories><subj-group subj-group-type="heading"><subject>Report</subject></subj-group></article-categories><title-group><article-title>Identification and Characterization of an Inborn Error of Metabolism Caused by Dihydrofolate Reductase Deficiency</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Banka</surname><given-names>Siddharth</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Blom</surname><given-names>Henk J.</given-names></name><xref rid="aff2" ref-type="aff">2</xref></contrib><contrib contrib-type="author"><name><surname>Walter</surname><given-names>John</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Aziz</surname><given-names>Majid</given-names></name><xref rid="aff3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Urquhart</surname><given-names>Jill</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Clouthier</surname><given-names>Christopher M.</given-names></name><xref rid="aff4" ref-type="aff">4</xref></contrib><contrib contrib-type="author"><name><surname>Rice</surname><given-names>Gillian I.</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>de Brouwer</surname><given-names>Arjan P.M.</given-names></name><xref rid="aff5" ref-type="aff">5</xref></contrib><contrib contrib-type="author"><name><surname>Hilton</surname><given-names>Emma</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Vassallo</surname><given-names>Grace</given-names></name><xref rid="aff3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Will</surname><given-names>Andrew</given-names></name><xref rid="aff6" ref-type="aff">6</xref></contrib><contrib contrib-type="author"><name><surname>Smith</surname><given-names>Desirée E.C.</given-names></name><xref rid="aff2" ref-type="aff">2</xref></contrib><contrib contrib-type="author"><name><surname>Smulders</surname><given-names>Yvo M.</given-names></name><xref rid="aff7" ref-type="aff">7</xref></contrib><contrib contrib-type="author"><name><surname>Wevers</surname><given-names>Ron A.</given-names></name><xref rid="aff8" ref-type="aff">8</xref></contrib><contrib contrib-type="author"><name><surname>Steinfeld</surname><given-names>Robert</given-names></name><xref rid="aff9" ref-type="aff">9</xref></contrib><contrib contrib-type="author"><name><surname>Heales</surname><given-names>Simon</given-names></name><xref rid="aff10" ref-type="aff">10</xref></contrib><contrib contrib-type="author"><name><surname>Crow</surname><given-names>Yanick J.</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Pelletier</surname><given-names>Joelle N.</given-names></name><xref rid="aff4" ref-type="aff">4</xref></contrib><contrib contrib-type="author"><name><surname>Jones</surname><given-names>Simon</given-names></name><email>simon.jones@cmft.nhs.uk</email><xref rid="aff1" ref-type="aff">1</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib><contrib contrib-type="author"><name><surname>Newman</surname><given-names>William G.</given-names></name><email>william.newman@manchester.ac.uk</email><xref rid="aff1" ref-type="aff">1</xref><xref rid="cor2" ref-type="corresp">∗∗</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester M13 9WL, UK</aff><aff id="aff2"><label>2</label>Metabolic Unit, Department of Clinical Chemistry, Institute for Cardiovascular Research, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands</aff><aff id="aff3"><label>3</label>Paediatric Neurology, MAHSC, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, UK</aff><aff id="aff4"><label>4</label>Département de Biochimie and Département de Chimie, Université de Montréal, Montréal, Québec H3C 3J7, Canada</aff><aff id="aff5"><label>5</label>Department of Human Genetics, Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands</aff><aff id="aff6"><label>6</label>Paediatric Haematology, MAHSC, St. Mary's Hospital, Central Manchester Foundation NHS Trust, Manchester M13 9WL, UK</aff><aff id="aff7"><label>7</label>Department of Internal Medicine, Institute for Cardiovascular Research, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands</aff><aff id="aff8"><label>8</label>Laboratory of Genetic Endocrine and Metabolic Diseases, Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands</aff><aff id="aff9"><label>9</label>Department of Pediatrics, University of Goettingen, Robert-Koch-Str. 40, D-37075 Goettingen, Germany</aff><aff id="aff10"><label>10</label>Neurometabolic Unit, National Hospital, Queen Square, Clinical and Molecular Genetics Unit, UCL Institute of Child Health & Enzyme and Metabolic Unit, Great Ormond Street Hospital, London WC1N 3JH, UK</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author <email>simon.jones@cmft.nhs.uk</email></corresp><corresp id="cor2"><label>∗∗</label>Corresponding author <email>william.newman@manchester.ac.uk</email></corresp></author-notes><pub-date pub-type="ppub"><day>11</day><month>2</month><year>2011</year></pub-date><volume>88</volume><issue>2</issue><fpage>216</fpage><lpage>225</lpage><history><date date-type="received"><day>24</day><month>11</month><year>2010</year></date><date date-type="rev-recd"><day>7</day><month>1</month><year>2011</year></date><date date-type="accepted"><day>11</day><month>1</month><year>2011</year></date></history><permissions><copyright-statement>© 2011 The American Society of Human Genetics. Published by Elsevier Ltd. All right reserved.</copyright-statement><copyright-year>2011</copyright-year><copyright-holder>The American Society of Human Genetics</copyright-holder></permissions><abstract><p>Dihydrofolate reductase (DHFR) is a critical enzyme in folate metabolism and an important target of antineoplastic, antimicrobial, and antiinflammatory drugs. We describe three individuals from two families with a recessive inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency due to a germline missense mutation in <italic>DHFR</italic>, resulting in profound enzyme deficiency. We show that cerebral folate levels, anemia, and pancytopenia of DHFR deficiency can be corrected by treatment with folinic acid. The characterization of this disorder provides evidence for the link between DHFR and metabolism of cerebral tetrahydrobiopterin, which is required for the formation of dopamine, serotonin, and norepinephrine and for the hydroxylation of aromatic amino acids. Moreover, this relationship provides insight into the role of folates in neurological conditions, including depression, Alzheimer disease, and Parkinson disease.</p></abstract></article-meta></front></pmc><affiliations><list><country><li>Allemagne</li><li>Canada</li><li>Pays-Bas</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Basse-Saxe</li><li>Grand Manchester</li></region><settlement><li>Göttingen</li><li>Manchester</li></settlement><orgName><li>Université de Manchester</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Banka, Siddharth" sort="Banka, Siddharth" uniqKey="Banka S" first="Siddharth" last="Banka">Siddharth Banka</name></region><name sortKey="Aziz, Majid" sort="Aziz, Majid" uniqKey="Aziz M" first="Majid" last="Aziz">Majid Aziz</name><name sortKey="Crow, Yanick J" sort="Crow, Yanick J" uniqKey="Crow Y" first="Yanick J." last="Crow">Yanick J. Crow</name><name sortKey="Heales, Simon" sort="Heales, Simon" uniqKey="Heales S" first="Simon" last="Heales">Simon Heales</name><name sortKey="Hilton, Emma" sort="Hilton, Emma" uniqKey="Hilton E" first="Emma" last="Hilton">Emma Hilton</name><name sortKey="Jones, Simon" sort="Jones, Simon" uniqKey="Jones S" first="Simon" last="Jones">Simon Jones</name><name sortKey="Newman, William G" sort="Newman, William G" uniqKey="Newman W" first="William G." last="Newman">William G. Newman</name><name sortKey="Rice, Gillian I" sort="Rice, Gillian I" uniqKey="Rice G" first="Gillian I." last="Rice">Gillian I. Rice</name><name sortKey="Urquhart, Jill" sort="Urquhart, Jill" uniqKey="Urquhart J" first="Jill" last="Urquhart">Jill Urquhart</name><name sortKey="Vassallo, Grace" sort="Vassallo, Grace" uniqKey="Vassallo G" first="Grace" last="Vassallo">Grace Vassallo</name><name sortKey="Walter, John" sort="Walter, John" uniqKey="Walter J" first="John" last="Walter">John Walter</name><name sortKey="Will, Andrew" sort="Will, Andrew" uniqKey="Will A" first="Andrew" last="Will">Andrew Will</name></country><country name="Pays-Bas"><noRegion><name sortKey="Blom, Henk J" sort="Blom, Henk J" uniqKey="Blom H" first="Henk J." last="Blom">Henk J. Blom</name></noRegion><name sortKey="De Brouwer, Arjan P M" sort="De Brouwer, Arjan P M" uniqKey="De Brouwer A" first="Arjan P. M." last="De Brouwer">Arjan P. M. De Brouwer</name><name sortKey="Smith, Desiree E C" sort="Smith, Desiree E C" uniqKey="Smith D" first="Desirée E. C." last="Smith">Desirée E. C. Smith</name><name sortKey="Smulders, Yvo M" sort="Smulders, Yvo M" uniqKey="Smulders Y" first="Yvo M." last="Smulders">Yvo M. Smulders</name><name sortKey="Wevers, Ron A" sort="Wevers, Ron A" uniqKey="Wevers R" first="Ron A." last="Wevers">Ron A. Wevers</name></country><country name="Canada"><noRegion><name sortKey="Clouthier, Christopher M" sort="Clouthier, Christopher M" uniqKey="Clouthier C" first="Christopher M." last="Clouthier">Christopher M. Clouthier</name></noRegion><name sortKey="Pelletier, Joelle N" sort="Pelletier, Joelle N" uniqKey="Pelletier J" first="Joelle N." last="Pelletier">Joelle N. Pelletier</name></country><country name="Allemagne"><region name="Basse-Saxe"><name sortKey="Steinfeld, Robert" sort="Steinfeld, Robert" uniqKey="Steinfeld R" first="Robert" last="Steinfeld">Robert Steinfeld</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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