Clinical features of facioscapulohumeral muscular dystrophy 2

Autores
De Greef, J. C.; Lemmers, R. J. L. F.; Camaño, P.; Day, J. W.; Sacconi, S.; Dunand, M.; Van Engelen, B. G. M.; Kiuru Enari, S.; Padberg, G. W.; Rosa, Alberto Luis; Desnuelle, C.; Spuler, S.; Tarnopolsky, M.; Venance, S. L.; Frants, R. R.; Van Der Maarel, S. M.; Tawil, R.
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objective: In some 5% of patients with facioscapulohumeral muscular dystrophy (FSHD), no D4Z4 repeat contraction on chromosome 4q35 is observed. Such patients, termed patients with FSHD2, show loss of DNA methylation and heterochromatin markers at the D4Z4 repeat that are similar to patients with D4Z4 contractions (FSHD1). This commonality suggests that a change in D4Z4 chromatin structure unifies FSHD1 and FSHD2. The aim of our study was to critically evaluate the clinical features in patients with FSHD2 in order to establish whether these patients are phenotypically identical to FSHD1 and to establish the effects of the (epi-) genotype on the phenotype. Methods: This cross-sectional study studied 33 patients with FSHD2 from 27 families, the largest cohort described to date. All patients were clinically assessed using a standardized clinical evaluation form. Genotype analysis was performed by pulsed field gel electrophoresis and PCR; D4Z4 methylation was studied by methylation-sensitive Southern blot analysis. Results: FSHD2 is identical to FSHD1 in its clinical presentation. Notable differences include a higher incidence (67%) of sporadic cases and the absence of gender differences in disease severity in FSHD2. Overall, average disease severity in FSHD2 was similar to that reported in FSHD1 and was not influenced by D4Z4 repeat size. In FSHD2, a small effect of the degree of hypomethylation on disease severity was observed. Conclusions: Clinically, patients with FSHD2 are indistinguishable from patients with FSHD1. The present data suggest that FSHD1 and FSHD2 are the result of the same pathophysiologic process. METHODS: This cross-sectional study studied 33 patients with FSHD2 from 27 families, the largest cohort described to date. All patients were clinically assessed using a standardized clinical evaluation form. Genotype analysis was performed by pulsed field gel electrophoresis and PCR; D4Z4 methylation was studied by methylation-sensitive Southern blot analysis. RESULTS: FSHD2 is identical to FSHD1 in its clinical presentation. Notable differences include a higher incidence (67%) of sporadic cases and the absence of gender differences in disease severity in FSHD2. Overall, average disease severity in FSHD2 was similar to that reported in FSHD1 and was not influenced by D4Z4 repeat size. In FSHD2, a small effect of the degree of hypomethylation on disease severity was observed. CONCLUSIONS: Clinically, patients with FSHD2 are indistinguishable from patients with FSHD1. The present data suggest that FSHD1 and FSHD2 are the result of the same pathophysiologic process.
Fil: De Greef, J. C.. Leiden University; Países Bajos
Fil: Lemmers, R. J. L. F.. Leiden University; Países Bajos
Fil: Camaño, P.. Donostia International Physic Center; España. Instituto de Salud Carlos III; España
Fil: Day, J. W.. University of Minnesota; Estados Unidos
Fil: Sacconi, S.. Centre National de la Recherche Scientifique; Francia. Universite Nice; Francia
Fil: Dunand, M.. Centre Hospitalier Universitaire Vaudois; Suiza. Universite de Lausanne; Suiza
Fil: Van Engelen, B. G. M.. Radboud Universiteit Nijmegen; Países Bajos
Fil: Kiuru Enari, S.. Helsinki University Central Hospital; Finlandia
Fil: Padberg, G. W.. Radboud Universiteit Nijmegen; Países Bajos
Fil: Rosa, Alberto Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Fundación Allende; Argentina. Sanatorio Allende; Argentina
Fil: Desnuelle, C.. Centre National de la Recherche Scientifique; Francia. Universite Nice; Francia
Fil: Spuler, S.. Charité University Medicine Berlin; Alemania
Fil: Tarnopolsky, M.. Mc Master University; Canadá
Fil: Venance, S. L.. London Health Sciences Centre; Canadá
Fil: Frants, R. R.. Leiden University; Países Bajos
Fil: Van Der Maarel, S. M.. Leiden University; Países Bajos
Fil: Tawil, R.. University of Rochester Medical Center; Estados Unidos
Materia
FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY
LOCUS 4Q35
D4Z4 REPEAT INDEPENDENT CONTRACTION
FSHD2
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/189153

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network_name_str CONICET Digital (CONICET)
spelling Clinical features of facioscapulohumeral muscular dystrophy 2De Greef, J. C.Lemmers, R. J. L. F.Camaño, P.Day, J. W.Sacconi, S.Dunand, M.Van Engelen, B. G. M.Kiuru Enari, S.Padberg, G. W.Rosa, Alberto LuisDesnuelle, C.Spuler, S.Tarnopolsky, M.Venance, S. L.Frants, R. R.Van Der Maarel, S. M.Tawil, R.FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHYLOCUS 4Q35D4Z4 REPEAT INDEPENDENT CONTRACTIONFSHD2https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Objective: In some 5% of patients with facioscapulohumeral muscular dystrophy (FSHD), no D4Z4 repeat contraction on chromosome 4q35 is observed. Such patients, termed patients with FSHD2, show loss of DNA methylation and heterochromatin markers at the D4Z4 repeat that are similar to patients with D4Z4 contractions (FSHD1). This commonality suggests that a change in D4Z4 chromatin structure unifies FSHD1 and FSHD2. The aim of our study was to critically evaluate the clinical features in patients with FSHD2 in order to establish whether these patients are phenotypically identical to FSHD1 and to establish the effects of the (epi-) genotype on the phenotype. Methods: This cross-sectional study studied 33 patients with FSHD2 from 27 families, the largest cohort described to date. All patients were clinically assessed using a standardized clinical evaluation form. Genotype analysis was performed by pulsed field gel electrophoresis and PCR; D4Z4 methylation was studied by methylation-sensitive Southern blot analysis. Results: FSHD2 is identical to FSHD1 in its clinical presentation. Notable differences include a higher incidence (67%) of sporadic cases and the absence of gender differences in disease severity in FSHD2. Overall, average disease severity in FSHD2 was similar to that reported in FSHD1 and was not influenced by D4Z4 repeat size. In FSHD2, a small effect of the degree of hypomethylation on disease severity was observed. Conclusions: Clinically, patients with FSHD2 are indistinguishable from patients with FSHD1. The present data suggest that FSHD1 and FSHD2 are the result of the same pathophysiologic process. METHODS: This cross-sectional study studied 33 patients with FSHD2 from 27 families, the largest cohort described to date. All patients were clinically assessed using a standardized clinical evaluation form. Genotype analysis was performed by pulsed field gel electrophoresis and PCR; D4Z4 methylation was studied by methylation-sensitive Southern blot analysis. RESULTS: FSHD2 is identical to FSHD1 in its clinical presentation. Notable differences include a higher incidence (67%) of sporadic cases and the absence of gender differences in disease severity in FSHD2. Overall, average disease severity in FSHD2 was similar to that reported in FSHD1 and was not influenced by D4Z4 repeat size. In FSHD2, a small effect of the degree of hypomethylation on disease severity was observed. CONCLUSIONS: Clinically, patients with FSHD2 are indistinguishable from patients with FSHD1. The present data suggest that FSHD1 and FSHD2 are the result of the same pathophysiologic process.Fil: De Greef, J. C.. Leiden University; Países BajosFil: Lemmers, R. J. L. F.. Leiden University; Países BajosFil: Camaño, P.. Donostia International Physic Center; España. Instituto de Salud Carlos III; EspañaFil: Day, J. W.. University of Minnesota; Estados UnidosFil: Sacconi, S.. Centre National de la Recherche Scientifique; Francia. Universite Nice; FranciaFil: Dunand, M.. Centre Hospitalier Universitaire Vaudois; Suiza. Universite de Lausanne; SuizaFil: Van Engelen, B. G. M.. Radboud Universiteit Nijmegen; Países BajosFil: Kiuru Enari, S.. Helsinki University Central Hospital; FinlandiaFil: Padberg, G. W.. Radboud Universiteit Nijmegen; Países BajosFil: Rosa, Alberto Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Fundación Allende; Argentina. Sanatorio Allende; ArgentinaFil: Desnuelle, C.. Centre National de la Recherche Scientifique; Francia. Universite Nice; FranciaFil: Spuler, S.. Charité University Medicine Berlin; AlemaniaFil: Tarnopolsky, M.. Mc Master University; CanadáFil: Venance, S. L.. London Health Sciences Centre; CanadáFil: Frants, R. R.. Leiden University; Países BajosFil: Van Der Maarel, S. M.. Leiden University; Países BajosFil: Tawil, R.. University of Rochester Medical Center; Estados UnidosLippincott Williams2010-10-26info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/189153De Greef, J. C.; Lemmers, R. J. L. F.; Camaño, P.; Day, J. W.; Sacconi, S.; et al.; Clinical features of facioscapulohumeral muscular dystrophy 2; Lippincott Williams; Neurology; 75; 17; 26-10-2010; 1548-15540028-38781526-632XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://n.neurology.org/content/75/17/1548info:eu-repo/semantics/altIdentifier/doi/10.1212/WNL.0b013e3181f96175info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:01:44Zoai:ri.conicet.gov.ar:11336/189153instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:01:44.294CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Clinical features of facioscapulohumeral muscular dystrophy 2
title Clinical features of facioscapulohumeral muscular dystrophy 2
spellingShingle Clinical features of facioscapulohumeral muscular dystrophy 2
De Greef, J. C.
FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY
LOCUS 4Q35
D4Z4 REPEAT INDEPENDENT CONTRACTION
FSHD2
title_short Clinical features of facioscapulohumeral muscular dystrophy 2
title_full Clinical features of facioscapulohumeral muscular dystrophy 2
title_fullStr Clinical features of facioscapulohumeral muscular dystrophy 2
title_full_unstemmed Clinical features of facioscapulohumeral muscular dystrophy 2
title_sort Clinical features of facioscapulohumeral muscular dystrophy 2
dc.creator.none.fl_str_mv De Greef, J. C.
Lemmers, R. J. L. F.
Camaño, P.
Day, J. W.
Sacconi, S.
Dunand, M.
Van Engelen, B. G. M.
Kiuru Enari, S.
Padberg, G. W.
Rosa, Alberto Luis
Desnuelle, C.
Spuler, S.
Tarnopolsky, M.
Venance, S. L.
Frants, R. R.
Van Der Maarel, S. M.
Tawil, R.
author De Greef, J. C.
author_facet De Greef, J. C.
Lemmers, R. J. L. F.
Camaño, P.
Day, J. W.
Sacconi, S.
Dunand, M.
Van Engelen, B. G. M.
Kiuru Enari, S.
Padberg, G. W.
Rosa, Alberto Luis
Desnuelle, C.
Spuler, S.
Tarnopolsky, M.
Venance, S. L.
Frants, R. R.
Van Der Maarel, S. M.
Tawil, R.
author_role author
author2 Lemmers, R. J. L. F.
Camaño, P.
Day, J. W.
Sacconi, S.
Dunand, M.
Van Engelen, B. G. M.
Kiuru Enari, S.
Padberg, G. W.
Rosa, Alberto Luis
Desnuelle, C.
Spuler, S.
Tarnopolsky, M.
Venance, S. L.
Frants, R. R.
Van Der Maarel, S. M.
Tawil, R.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY
LOCUS 4Q35
D4Z4 REPEAT INDEPENDENT CONTRACTION
FSHD2
topic FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY
LOCUS 4Q35
D4Z4 REPEAT INDEPENDENT CONTRACTION
FSHD2
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objective: In some 5% of patients with facioscapulohumeral muscular dystrophy (FSHD), no D4Z4 repeat contraction on chromosome 4q35 is observed. Such patients, termed patients with FSHD2, show loss of DNA methylation and heterochromatin markers at the D4Z4 repeat that are similar to patients with D4Z4 contractions (FSHD1). This commonality suggests that a change in D4Z4 chromatin structure unifies FSHD1 and FSHD2. The aim of our study was to critically evaluate the clinical features in patients with FSHD2 in order to establish whether these patients are phenotypically identical to FSHD1 and to establish the effects of the (epi-) genotype on the phenotype. Methods: This cross-sectional study studied 33 patients with FSHD2 from 27 families, the largest cohort described to date. All patients were clinically assessed using a standardized clinical evaluation form. Genotype analysis was performed by pulsed field gel electrophoresis and PCR; D4Z4 methylation was studied by methylation-sensitive Southern blot analysis. Results: FSHD2 is identical to FSHD1 in its clinical presentation. Notable differences include a higher incidence (67%) of sporadic cases and the absence of gender differences in disease severity in FSHD2. Overall, average disease severity in FSHD2 was similar to that reported in FSHD1 and was not influenced by D4Z4 repeat size. In FSHD2, a small effect of the degree of hypomethylation on disease severity was observed. Conclusions: Clinically, patients with FSHD2 are indistinguishable from patients with FSHD1. The present data suggest that FSHD1 and FSHD2 are the result of the same pathophysiologic process. METHODS: This cross-sectional study studied 33 patients with FSHD2 from 27 families, the largest cohort described to date. All patients were clinically assessed using a standardized clinical evaluation form. Genotype analysis was performed by pulsed field gel electrophoresis and PCR; D4Z4 methylation was studied by methylation-sensitive Southern blot analysis. RESULTS: FSHD2 is identical to FSHD1 in its clinical presentation. Notable differences include a higher incidence (67%) of sporadic cases and the absence of gender differences in disease severity in FSHD2. Overall, average disease severity in FSHD2 was similar to that reported in FSHD1 and was not influenced by D4Z4 repeat size. In FSHD2, a small effect of the degree of hypomethylation on disease severity was observed. CONCLUSIONS: Clinically, patients with FSHD2 are indistinguishable from patients with FSHD1. The present data suggest that FSHD1 and FSHD2 are the result of the same pathophysiologic process.
Fil: De Greef, J. C.. Leiden University; Países Bajos
Fil: Lemmers, R. J. L. F.. Leiden University; Países Bajos
Fil: Camaño, P.. Donostia International Physic Center; España. Instituto de Salud Carlos III; España
Fil: Day, J. W.. University of Minnesota; Estados Unidos
Fil: Sacconi, S.. Centre National de la Recherche Scientifique; Francia. Universite Nice; Francia
Fil: Dunand, M.. Centre Hospitalier Universitaire Vaudois; Suiza. Universite de Lausanne; Suiza
Fil: Van Engelen, B. G. M.. Radboud Universiteit Nijmegen; Países Bajos
Fil: Kiuru Enari, S.. Helsinki University Central Hospital; Finlandia
Fil: Padberg, G. W.. Radboud Universiteit Nijmegen; Países Bajos
Fil: Rosa, Alberto Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Fundación Allende; Argentina. Sanatorio Allende; Argentina
Fil: Desnuelle, C.. Centre National de la Recherche Scientifique; Francia. Universite Nice; Francia
Fil: Spuler, S.. Charité University Medicine Berlin; Alemania
Fil: Tarnopolsky, M.. Mc Master University; Canadá
Fil: Venance, S. L.. London Health Sciences Centre; Canadá
Fil: Frants, R. R.. Leiden University; Países Bajos
Fil: Van Der Maarel, S. M.. Leiden University; Países Bajos
Fil: Tawil, R.. University of Rochester Medical Center; Estados Unidos
description Objective: In some 5% of patients with facioscapulohumeral muscular dystrophy (FSHD), no D4Z4 repeat contraction on chromosome 4q35 is observed. Such patients, termed patients with FSHD2, show loss of DNA methylation and heterochromatin markers at the D4Z4 repeat that are similar to patients with D4Z4 contractions (FSHD1). This commonality suggests that a change in D4Z4 chromatin structure unifies FSHD1 and FSHD2. The aim of our study was to critically evaluate the clinical features in patients with FSHD2 in order to establish whether these patients are phenotypically identical to FSHD1 and to establish the effects of the (epi-) genotype on the phenotype. Methods: This cross-sectional study studied 33 patients with FSHD2 from 27 families, the largest cohort described to date. All patients were clinically assessed using a standardized clinical evaluation form. Genotype analysis was performed by pulsed field gel electrophoresis and PCR; D4Z4 methylation was studied by methylation-sensitive Southern blot analysis. Results: FSHD2 is identical to FSHD1 in its clinical presentation. Notable differences include a higher incidence (67%) of sporadic cases and the absence of gender differences in disease severity in FSHD2. Overall, average disease severity in FSHD2 was similar to that reported in FSHD1 and was not influenced by D4Z4 repeat size. In FSHD2, a small effect of the degree of hypomethylation on disease severity was observed. Conclusions: Clinically, patients with FSHD2 are indistinguishable from patients with FSHD1. The present data suggest that FSHD1 and FSHD2 are the result of the same pathophysiologic process. METHODS: This cross-sectional study studied 33 patients with FSHD2 from 27 families, the largest cohort described to date. All patients were clinically assessed using a standardized clinical evaluation form. Genotype analysis was performed by pulsed field gel electrophoresis and PCR; D4Z4 methylation was studied by methylation-sensitive Southern blot analysis. RESULTS: FSHD2 is identical to FSHD1 in its clinical presentation. Notable differences include a higher incidence (67%) of sporadic cases and the absence of gender differences in disease severity in FSHD2. Overall, average disease severity in FSHD2 was similar to that reported in FSHD1 and was not influenced by D4Z4 repeat size. In FSHD2, a small effect of the degree of hypomethylation on disease severity was observed. CONCLUSIONS: Clinically, patients with FSHD2 are indistinguishable from patients with FSHD1. The present data suggest that FSHD1 and FSHD2 are the result of the same pathophysiologic process.
publishDate 2010
dc.date.none.fl_str_mv 2010-10-26
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/189153
De Greef, J. C.; Lemmers, R. J. L. F.; Camaño, P.; Day, J. W.; Sacconi, S.; et al.; Clinical features of facioscapulohumeral muscular dystrophy 2; Lippincott Williams; Neurology; 75; 17; 26-10-2010; 1548-1554
0028-3878
1526-632X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/189153
identifier_str_mv De Greef, J. C.; Lemmers, R. J. L. F.; Camaño, P.; Day, J. W.; Sacconi, S.; et al.; Clinical features of facioscapulohumeral muscular dystrophy 2; Lippincott Williams; Neurology; 75; 17; 26-10-2010; 1548-1554
0028-3878
1526-632X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://n.neurology.org/content/75/17/1548
info:eu-repo/semantics/altIdentifier/doi/10.1212/WNL.0b013e3181f96175
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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