Clinical and molecular phenotype of Aicardi-Goutieres syndrome
Por:
Rice G, Patrick T, Parmar R, Taylor CF, Aeby A, Aicardi J, Artuch-Iriberri R, Montalto SA, Bacino CA, Barroso B, Baxter P, Benko WS, Bergmann C, Bertini E, Biancheri R, Blair EM, Blau N, Bonthron DT, Briggs T, Brueton LA, Brunner HG, Burke CJ, Carr IM, Carvalho DR, Chandler KE, Christen HJ, Corry PC, Cowan FM, Cox H, D'Arrigo S, Dean J, De Laet C, De Praeter C, Dery C, Ferrie CD, Flintoff K, Frints SG, Garcia-Cazorla A, Gener B, Goizet C, Goutieres F, Green AJ, Guet A, Hamel BC, Hayward BE, Heiberg A, Hennekam RC, Husson M, Jackson AP, Jayatunga R, Jiang YH, Kant SG, Kao A, King MD, Kingston HM, Klepper J, van der Knaap MS, Kornberg AJ, Kotzot D, Kratzer W, Lacombe D, Lagae L, Landrieu PG, Lanzi G, Leitch A, Lim MJ, Livingston JH, Lourenco CM, Lyall EG, Lynch SA, Lyons MJ, Marom D, McClure JP, McWilliam R, Melancon SB, Mewasingh LD, Moutard ML, Nischal KK, Ostergaard JR, Prendiville J, Rasmussen M, Rogers RC, Roland D, Rosser EM, Rostasy K, Roubertie A, Sanchis A, Schiffmann R, Scholl-Burgi S, Seal S, Shalev SA, Corcoles CS, Sinha GP, Soler D, Spiegel R, Stephenson JB, Tacke U, Tan TY, Till M, Tolmie JL, Tomlin P, Vagnarelli F, Valente EM, Van Coster RN, Van der Aa N, Vanderver A, Vles JS, Voit T, Wassmer E, Weschke B, Whiteford ML, Willemsen MA, Zankl A, Zuberi SM, Orcesi S, Fazzi E, Lebon P and Crow YJ
Publicada:
1 oct 2007
Resumen:
Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-> 5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later- onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P = .001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation- screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS- causing gene remains to be identified.
Filiaciones:
St James Univ Hosp, Leeds Inst Mol Med, Leeds LS9 7TF, W Yorkshire, England.
St James Univ Hosp, Dept Clin Genet, DNA Lab, Leeds LS9 7TF, W Yorkshire, England.
Canc Res UK, Mutat Detect Facil, Leeds, W Yorkshire, England.
Leeds Gen Infirm, Dept Paediat Neurol, Leeds, W Yorkshire, England.
Erasme Univ Hosp, Dept Paediat Neurol, Brussels, Belgium.
Childrens Hosp Queen Fabiola, Brussels, Belgium.
Hop Trousseau, Serv Neuropediat, F-75571 Paris, France.
Hop Trousseau, Dept Paediat Neurol, F-75571 Paris, France.
Hop Bicetre, Paediat Neurol Dept, Paris, France.
Grp Hosp Pitie Salpetriere, Inst Myol, F-75634 Paris, France.
Hop Cochin St Vincent de Paul, Serv Virol, Paris, France.
Hosp St Joan Deu Ciberer, Dept Clin Biochem, Barcelona, Spain.
Hosp St Joan Deu Ciberer, Dept Barcelona Pediat Neurol, Barcelona, Spain.
St Lukes Hosp, Dept Paediat, Guardamangia, Malta.
Baylor Coll Med, Dept Human Mol Genet, Houston, TX 77030 USA.
Ctr Hosp, Ser Neurol, Pau, France.
Sheffield Childrens Hosp, Dept Paediat, Sheffield S10 2TH, S Yorkshire, England.
Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, Natl Inst Hlth, Bethesda, MD USA.
Univ Aachen, Rhein Westfal TH Aachen, Dept Human Genet, D-5100 Aachen, Germany.
Bambino Gesu Childrens Res Hosp, Mol Med Unit, Rome, Italy.
Mendel Inst Med Genet & Twin Res, IRCCS, Rome, Italy.
G Gaslini Inst Children, Muscular & Neurodegeberat Dis Unit, Genoa, Italy.
Churchill Hosp, Dept Clin Genet, Oxford OX3 7LJ, England.
Univ Childrens Hosp, Div Clin Chem & Biochem, Zurich, Switzerland.
Birmingham Womens Hosp, Clin Genet Unit, Birmingham, W Midlands, England.
Sandwell & W Birmingham NHS Trust, Dept Paediat, Birmingham, W Midlands, England.
Birmingham Childrens Hosp, Dept Neurol, Birmingham, W Midlands, England.
Radboud Univ Nijmegen, Dept Human Genet, Nijmegen, Netherlands.
Radboud Univ Nijmegen, Dept Pediat Neurol, Nijmegen, Netherlands.
Royal Childrens Hosp, Dept Pediat Neurol, Brisbane, Qld, Australia.
Royal Childrens Hosp, Genet Hlth Queensland, Brisbane, Qld, Australia.
Univ Estadual Sao Paulo, Serv Aconselhamento Genet, Botucatu, SP, Brazil.
St Marys Hosp, Acad Unit Med Genet, Manchester M13 0JH, Lancs, England.
Kinderkrankenhaus Bult, Hannover, Germany.
Bradford Natl Hlth Serv NHS Trust, Dept Paediat, Bradford, W Yorkshire, England.
Fdn Ist Neurol C Besta, Dev Neurol Dept, Milan, Italy.
Grampian Clin Genet Ctr, Aberdeen, Scotland.
State Univ Ghent Hosp, Dept Neonatol, Ghent, Belgium.
State Univ Ghent Hosp, Dept Pediat, Ghent, Belgium.
Maastricht Univ Hosp, Dept Clin Genet, Maastricht, Netherlands.
Maastricht Univ Hosp, Dept Neurol, Maastricht, Netherlands.
Great Ormond St Hosp Sick Children, Imperial Coll, Dept Paediat & Imaging Sci, London, England.
Great Ormond St Hosp Sick Children, St Marys NHS Trust, London, England.
Great Ormond St Hosp Sick Children, Dept Ophthalmol, London, England.
Great Ormond St Hosp Sick Children, NE Thames Reg Genet Serv, London, England.
Evelina Childrens Hosp, London, England.
St Thomas NHS Trust, London, England.
Univ Laval, Sch Med, Dept Paediat, Quebec City, PQ, Canada.
Hosp Cruces, Clin Genet Unit, Baracaldo, Spain.
CHU Pellegrin Enfants, Gen Med Serv, Bordeaux, France.
CHU Pellegrin Enfants, Unite Neurol Enfant & Adolescent, Bordeaux, France.
Our Ladys Hosp Sick Children, Natl Ctr Med Genet, Dublin, Ireland.
Childrens Univ Hosp, Dept Paediat Neurol, Dublin, Ireland.
Univ Oslo, Rikshosp, Radiumhosp, Dept Med Genet, N-0027 Oslo, Norway.
Univ Oslo, Rikshosp, Radiumhosp, Dept Paediat, N-0027 Oslo, Norway.
Vrije Univ Amsterdam, Ctr Med, Dept Child Neurol, Amsterdam, Netherlands.
Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands.
Oregon Hlth & Sci Univ, Div Pediat Neurol, Portland, OR 97201 USA.
Klinikum Aschaffenburg, Aschaffenburg, Germany.
Royal Childrens Hosp, Dept Neurol, Parkville, Vic 3052, Australia.
Med Univ Innsbruck, Dept Med Genet, Div Clin Genet, Innsbruck, Austria.
Childrens Hosp Innsbruck, Dept Pediat, Div Pediat Neurol & Inborn Errors Metab, Innsbruck, Austria.
Klin Kinder & Jugendliche, Constance, Germany.
Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium.
IRCCS Casmiro Mondino Inst Neurol, Dept Child Neurol & Psychiat, Pavia, Italy.
Univ Sao Paulo, Dept Neurogenet, Ribeirao Preto, Brazil.
Greenwood Genet Ctr, Greenwood, SC 29646 USA.
Rabin Med Ctr, Raphael Racanati Genet Inst, Petah Tiqwa, Israel.
Crosshouse Hosp, Dept Paediat, Ayr, Scotland.
Royal Hosp Sick Children, Fraser Allander Neurosci Unit, Glasgow G3 8SJ, Lanark, Scotland.
Royal Hosp Sick Children, Duncan Guthrie Inst Med Genet, Glasgow G3 8SJ, Lanark, Scotland.
Montreal Childrens Hosp, Div Med Genet, Montreal, PQ H3H 1P3, Canada.
Univ Hosp Leicester NHS Trust, Dept Paediat Neurol, Leicester, Leics, England.
Aarhus Univ Hosp, DK-8000 Aarhus, Denmark.
British Columbia Childrens Hosp, Div Pediat Dermatol, Vancouver, BC, Canada.
Inst Pathol & Genet, Gosselies, Belgium.
Gui Chauliac Hosp, Pediat Neurol Dept, Montpellier, France.
Hosp Univ Doctor Peset, Serv Pediat, Valencia, Spain.
Technion Israel Inst Technol, Rappaport Fac Med, Haifa, Israel.
Haemek Med Ctr, Inst Genet, Afula, Israel.
Complejo Hosp Jean, Neuropediat Unit, Jean, Spain.
Manor Hosp, Dept Paediat, Walsall, W Midlands, England.
Univ Hosp, Div Neuropediat, Freiburg, Germany.
Royal Childrens Hosp, Genet Hlth Serv Victoria, Brisbane, Qld, Australia.
Hop Debrousse, Lyon, France.
Lancashire Teaching Hosp Trust, Preston, Lancs, England.
Arcispedale Santa Maria Nuova, Neonatal Intens Care Unit, Reggio Emilia, Italy.
Ctr Genet Med, Antwerp, Belgium.
Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
Humboldt Univ, Dept Neuropediat, Berlin, Germany.
St James Univ Hosp, Leeds Inst Mol Med, Leeds LS9 7TF, W Yorkshire, England
St James Univ Hosp, Dept Clin Genet, DNA Lab, Leeds LS9 7TF, W Yorkshire, England
Canc Res UK, Mutat Detect Facil, Leeds, W Yorkshire, England
Leeds Gen Infirm, Dept Paediat Neurol, Leeds, W Yorkshire, England
Erasme Univ Hosp, Dept Paediat Neurol, Brussels, Belgium
Childrens Hosp Queen Fabiola, Brussels, Belgium
Hop Trousseau, Serv Neuropediat, F-75571 Paris, France
Hop Trousseau, Dept Paediat Neurol, F-75571 Paris, France
Hop Bicetre, Paediat Neurol Dept, Paris, France
Grp Hosp Pitie Salpetriere, Inst Myol, F-75634 Paris, France
Hop Cochin St Vincent de Paul, Serv Virol, Paris, France
Hosp St Joan Deu Ciberer, Dept Clin Biochem, Barcelona, Spain
Hosp St Joan Deu Ciberer, Dept Barcelona Pediat Neurol, Barcelona, Spain
St Lukes Hosp, Dept Paediat, Guardamangia, Malta
Baylor Coll Med, Dept Human Mol Genet, Houston, TX 77030 USA
Ctr Hosp, Ser Neurol, Pau, France
Sheffield Childrens Hosp, Dept Paediat, Sheffield S10 2TH, S Yorkshire, England
Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, Natl Inst Hlth, Bethesda, MD USA
Univ Aachen, Rhein Westfal TH Aachen, Dept Human Genet, D-5100 Aachen, Germany
Bambino Gesu Childrens Res Hosp, Mol Med Unit, Rome, Italy
Mendel Inst Med Genet & Twin Res, IRCCS, Rome, Italy
G Gaslini Inst Children, Muscular & Neurodegeberat Dis Unit, Genoa, Italy
Churchill Hosp, Dept Clin Genet, Oxford OX3 7LJ, England
Univ Childrens Hosp, Div Clin Chem & Biochem, Zurich, Switzerland
Birmingham Womens Hosp, Clin Genet Unit, Birmingham, W Midlands, England
Sandwell & W Birmingham NHS Trust, Dept Paediat, Birmingham, W Midlands, England
Birmingham Childrens Hosp, Dept Neurol, Birmingham, W Midlands, England
Radboud Univ Nijmegen, Dept Human Genet, Nijmegen, Netherlands
Radboud Univ Nijmegen, Dept Pediat Neurol, Nijmegen, Netherlands
Royal Childrens Hosp, Dept Pediat Neurol, Brisbane, Qld, Australia
Royal Childrens Hosp, Genet Hlth Queensland, Brisbane, Qld, Australia
Univ Estadual Sao Paulo, Serv Aconselhamento Genet, Botucatu, SP, Brazil
St Marys Hosp, Acad Unit Med Genet, Manchester M13 0JH, Lancs, England
Kinderkrankenhaus Bult, Hannover, Germany
Bradford Natl Hlth Serv NHS Trust, Dept Paediat, Bradford, W Yorkshire, England
Fdn Ist Neurol C Besta, Dev Neurol Dept, Milan, Italy
Grampian Clin Genet Ctr, Aberdeen, Scotland
State Univ Ghent Hosp, Dept Neonatol, Ghent, Belgium
State Univ Ghent Hosp, Dept Pediat, Ghent, Belgium
Maastricht Univ Hosp, Dept Clin Genet, Maastricht, Netherlands
Maastricht Univ Hosp, Dept Neurol, Maastricht, Netherlands
Great Ormond St Hosp Sick Children, Imperial Coll, Dept Paediat & Imaging Sci, London, England
Great Ormond St Hosp Sick Children, St Marys NHS Trust, London, England
Great Ormond St Hosp Sick Children, Dept Ophthalmol, London, England
Great Ormond St Hosp Sick Children, NE Thames Reg Genet Serv, London, England
Evelina Childrens Hosp, London, England
St Thomas NHS Trust, London, England
Univ Laval, Sch Med, Dept Paediat, Quebec City, PQ, Canada
Hosp Cruces, Clin Genet Unit, Baracaldo, Spain
CHU Pellegrin Enfants, Gen Med Serv, Bordeaux, France
CHU Pellegrin Enfants, Unite Neurol Enfant & Adolescent, Bordeaux, France
Our Ladys Hosp Sick Children, Natl Ctr Med Genet, Dublin, Ireland
Childrens Univ Hosp, Dept Paediat Neurol, Dublin, Ireland
Univ Oslo, Rikshosp, Radiumhosp, Dept Med Genet, N-0027 Oslo, Norway
Univ Oslo, Rikshosp, Radiumhosp, Dept Paediat, N-0027 Oslo, Norway
Vrije Univ Amsterdam, Ctr Med, Dept Child Neurol, Amsterdam, Netherlands
Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland
Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands
Oregon Hlth & Sci Univ, Div Pediat Neurol, Portland, OR 97201 USA
Klinikum Aschaffenburg, Aschaffenburg, Germany
Royal Childrens Hosp, Dept Neurol, Parkville, Vic 3052, Australia
Med Univ Innsbruck, Dept Med Genet, Div Clin Genet, Innsbruck, Austria
Childrens Hosp Innsbruck, Dept Pediat, Div Pediat Neurol & Inborn Errors Metab, Innsbruck, Austria
Klin Kinder & Jugendliche, Constance, Germany
Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium
IRCCS Casmiro Mondino Inst Neurol, Dept Child Neurol & Psychiat, Pavia, Italy
Univ Sao Paulo, Dept Neurogenet, Ribeirao Preto, Brazil
Greenwood Genet Ctr, Greenwood, SC 29646 USA
Rabin Med Ctr, Raphael Racanati Genet Inst, Petah Tiqwa, Israel
Crosshouse Hosp, Dept Paediat, Ayr, Scotland
Royal Hosp Sick Children, Fraser Allander Neurosci Unit, Glasgow G3 8SJ, Lanark, Scotland
Royal Hosp Sick Children, Duncan Guthrie Inst Med Genet, Glasgow G3 8SJ, Lanark, Scotland
Montreal Childrens Hosp, Div Med Genet, Montreal, PQ H3H 1P3, Canada
Univ Hosp Leicester NHS Trust, Dept Paediat Neurol, Leicester, Leics, England
Aarhus Univ Hosp, DK-8000 Aarhus, Denmark
British Columbia Childrens Hosp, Div Pediat Dermatol, Vancouver, BC, Canada
Inst Pathol & Genet, Gosselies, Belgium
Gui Chauliac Hosp, Pediat Neurol Dept, Montpellier, France
Hosp Univ Doctor Peset, Serv Pediat, Valencia, Spain
Technion Israel Inst Technol, Rappaport Fac Med, Haifa, Israel
Haemek Med Ctr, Inst Genet, Afula, Israel
Complejo Hosp Jean, Neuropediat Unit, Jean, Spain
Manor Hosp, Dept Paediat, Walsall, W Midlands, England
Univ Hosp, Div Neuropediat, Freiburg, Germany
Royal Childrens Hosp, Genet Hlth Serv Victoria, Brisbane, Qld, Australia
Hop Debrousse, Lyon, France
Lancashire Teaching Hosp Trust, Preston, Lancs, England
Arcispedale Santa Maria Nuova, Neonatal Intens Care Unit, Reggio Emilia, Italy
Ctr Genet Med, Antwerp, Belgium
Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA
Humboldt Univ, Dept Neuropediat, Berlin, Germany
St James Univ Hosp, Leeds Inst Mol Med, Leeds LS9 7TF, W Yorkshire, England
St James Univ Hosp, Dept Clin Genet, DNA Lab, Leeds LS9 7TF, W Yorkshire, England
Canc Res UK, Mutat Detect Facil, Leeds, W Yorkshire, England
Leeds Gen Infirm, Dept Paediat Neurol, Leeds, W Yorkshire, England
Erasme Univ Hosp, Dept Paediat Neurol, Brussels, Belgium
Childrens Hosp Queen Fabiola, Brussels, Belgium
Hop Trousseau, Serv Neuropediat, F-75571 Paris, France
Hop Trousseau, Dept Paediat Neurol, F-75571 Paris, France
Hop Bicetre, Paediat Neurol Dept, Paris, France
Grp Hosp Pitie Salpetriere, Inst Myol, F-75634 Paris, France
Hop Cochin St Vincent de Paul, Serv Virol, Paris, France
Hosp St Joan Deu Ciberer, Dept Clin Biochem, Barcelona, Spain
Hosp St Joan Deu Ciberer, Dept Barcelona Pediat Neurol, Barcelona, Spain
St Lukes Hosp, Dept Paediat, Guardamangia, Malta
Baylor Coll Med, Dept Human Mol Genet, Houston, TX 77030 USA
Ctr Hosp, Ser Neurol, Pau, France
Sheffield Childrens Hosp, Dept Paediat, Sheffield S10 2TH, S Yorkshire, England
Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, Natl Inst Hlth, Bethesda, MD USA
Univ Aachen, Rhein Westfal TH Aachen, Dept Human Genet, D-5100 Aachen, Germany
Bambino Gesu Childrens Res Hosp, Mol Med Unit, Rome, Italy
Mendel Inst Med Genet & Twin Res, IRCCS, Rome, Italy
G Gaslini Inst Children, Muscular & Neurodegeberat Dis Unit, Genoa, Italy
Churchill Hosp, Dept Clin Genet, Oxford OX3 7LJ, England
Univ Childrens Hosp, Div Clin Chem & Biochem, Zurich, Switzerland
Birmingham Womens Hosp, Clin Genet Unit, Birmingham, W Midlands, England
Sandwell & W Birmingham NHS Trust, Dept Paediat, Birmingham, W Midlands, England
Birmingham Childrens Hosp, Dept Neurol, Birmingham, W Midlands, England
Radboud Univ Nijmegen, Dept Human Genet, Nijmegen, Netherlands
Radboud Univ Nijmegen, Dept Pediat Neurol, Nijmegen, Netherlands
Royal Childrens Hosp, Dept Pediat Neurol, Brisbane, Qld, Australia
Royal Childrens Hosp, Genet Hlth Queensland, Brisbane, Qld, Australia
Univ Estadual Sao Paulo, Serv Aconselhamento Genet, Botucatu, SP, Brazil
St Marys Hosp, Acad Unit Med Genet, Manchester M13 0JH, Lancs, England
Kinderkrankenhaus Bult, Hannover, Germany
Bradford Natl Hlth Serv NHS Trust, Dept Paediat, Bradford, W Yorkshire, England
Fdn Ist Neurol C Besta, Dev Neurol Dept, Milan, Italy
Grampian Clin Genet Ctr, Aberdeen, Scotland
State Univ Ghent Hosp, Dept Neonatol, Ghent, Belgium
State Univ Ghent Hosp, Dept Pediat, Ghent, Belgium
Maastricht Univ Hosp, Dept Clin Genet, Maastricht, Netherlands
Maastricht Univ Hosp, Dept Neurol, Maastricht, Netherlands
Great Ormond St Hosp Sick Children, Imperial Coll, Dept Paediat & Imaging Sci, London, England
Great Ormond St Hosp Sick Children, St Marys NHS Trust, London, England
Great Ormond St Hosp Sick Children, Dept Ophthalmol, London, England
Great Ormond St Hosp Sick Children, NE Thames Reg Genet Serv, London, England
Evelina Childrens Hosp, London, England
St Thomas NHS Trust, London, England
Univ Laval, Sch Med, Dept Paediat, Quebec City, PQ, Canada
Hosp Cruces, Clin Genet Unit, Baracaldo, Spain
CHU Pellegrin Enfants, Gen Med Serv, Bordeaux, France
CHU Pellegrin Enfants, Unite Neurol Enfant & Adolescent, Bordeaux, France
Our Ladys Hosp Sick Children, Natl Ctr Med Genet, Dublin, Ireland
Childrens Univ Hosp, Dept Paediat Neurol, Dublin, Ireland
Univ Oslo, Rikshosp, Radiumhosp, Dept Med Genet, N-0027 Oslo, Norway
Univ Oslo, Rikshosp, Radiumhosp, Dept Paediat, N-0027 Oslo, Norway
Vrije Univ Amsterdam, Ctr Med, Dept Child Neurol, Amsterdam, Netherlands
Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland
Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands
Oregon Hlth & Sci Univ, Div Pediat Neurol, Portland, OR 97201 USA
Klinikum Aschaffenburg, Aschaffenburg, Germany
Royal Childrens Hosp, Dept Neurol, Parkville, Vic 3052, Australia
Med Univ Innsbruck, Dept Med Genet, Div Clin Genet, Innsbruck, Austria
Childrens Hosp Innsbruck, Dept Pediat, Div Pediat Neurol & Inborn Errors Metab, Innsbruck, Austria
Klin Kinder & Jugendliche, Constance, Germany
Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium
IRCCS Casmiro Mondino Inst Neurol, Dept Child Neurol & Psychiat, Pavia, Italy
Univ Sao Paulo, Dept Neurogenet, Ribeirao Preto, Brazil
Greenwood Genet Ctr, Greenwood, SC 29646 USA
Rabin Med Ctr, Raphael Racanati Genet Inst, Petah Tiqwa, Israel
Crosshouse Hosp, Dept Paediat, Ayr, Scotland
Royal Hosp Sick Children, Fraser Allander Neurosci Unit, Glasgow G3 8SJ, Lanark, Scotland
Royal Hosp Sick Children, Duncan Guthrie Inst Med Genet, Glasgow G3 8SJ, Lanark, Scotland
Montreal Childrens Hosp, Div Med Genet, Montreal, PQ H3H 1P3, Canada
Univ Hosp Leicester NHS Trust, Dept Paediat Neurol, Leicester, Leics, England
Aarhus Univ Hosp, DK-8000 Aarhus, Denmark
British Columbia Childrens Hosp, Div Pediat Dermatol, Vancouver, BC, Canada
Inst Pathol & Genet, Gosselies, Belgium
Gui Chauliac Hosp, Pediat Neurol Dept, Montpellier, France
Hosp Univ Doctor Peset, Serv Pediat, Valencia, Spain
Technion Israel Inst Technol, Rappaport Fac Med, Haifa, Israel
Haemek Med Ctr, Inst Genet, Afula, Israel
Complejo Hosp Jean, Neuropediat Unit, Jean, Spain
Manor Hosp, Dept Paediat, Walsall, W Midlands, England
Univ Hosp, Div Neuropediat, Freiburg, Germany
Royal Childrens Hosp, Genet Hlth Serv Victoria, Brisbane, Qld, Australia
Hop Debrousse, Lyon, France
Lancashire Teaching Hosp Trust, Preston, Lancs, England
Arcispedale Santa Maria Nuova, Neonatal Intens Care Unit, Reggio Emilia, Italy
Ctr Genet Med, Antwerp, Belgium
Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA
Humboldt Univ, Dept Neuropediat, Berlin, Germany
Green Submitted, Green Published, Bronze
|