LAMA2 gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypes
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.17/3495 |
Resumo: | Congenital muscular dystrophy type 1A (MDC1A) is one of the main subtypes of early-onset muscle disease, caused by disease-associated variants in the laminin-α2 (LAMA2) gene. MDC1A usually presents as a severe neonatal hypotonia and failure to thrive. Muscle weakness compromises normal motor development, leading to the inability to sit unsupported or to walk independently. The phenotype associated with LAMA2 defects has been expanded to include milder and atypical cases, being now collectively known as LAMA2-related muscular dystrophies (LAMA2-MD). Through an international multicenter collaborative effort, 61 new LAMA2 disease-associated variants were identified in 86 patients, representing the largest number of patients and new disease-causing variants in a single report. The collaborative variant collection was supported by the LOVD-powered LAMA2 gene variant database (https://www.LOVD.nl/LAMA2), updated as part of this work. As of December 2017, the database contains 486 unique LAMA2 variants (309 disease-associated), obtained from direct submissions and literature reports. Database content was systematically reviewed and further insights concerning LAMA2-MD are presented. We focus on the impact of missense changes, especially the c.2461A > C (p.Thr821Pro) variant and its association with late-onset LAMA2-MD. Finally, we report diagnostically challenging cases, highlighting the relevance of modern genetic analysis in the characterization of clinically heterogeneous muscle diseases. |
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LAMA2 gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypesAllelesBiomarkersBrainComputational BiologyDatabases, Nucleic AcidGene FrequencyGenetic VariationGenotypeHumansImmunohistochemistryLamininMagnetic Resonance ImagingMuscular DystrophiesGenetic Association StudiesMutationPhenotypeHDE GENHDE NEU PEDCongenital muscular dystrophy type 1A (MDC1A) is one of the main subtypes of early-onset muscle disease, caused by disease-associated variants in the laminin-α2 (LAMA2) gene. MDC1A usually presents as a severe neonatal hypotonia and failure to thrive. Muscle weakness compromises normal motor development, leading to the inability to sit unsupported or to walk independently. The phenotype associated with LAMA2 defects has been expanded to include milder and atypical cases, being now collectively known as LAMA2-related muscular dystrophies (LAMA2-MD). Through an international multicenter collaborative effort, 61 new LAMA2 disease-associated variants were identified in 86 patients, representing the largest number of patients and new disease-causing variants in a single report. The collaborative variant collection was supported by the LOVD-powered LAMA2 gene variant database (https://www.LOVD.nl/LAMA2), updated as part of this work. As of December 2017, the database contains 486 unique LAMA2 variants (309 disease-associated), obtained from direct submissions and literature reports. Database content was systematically reviewed and further insights concerning LAMA2-MD are presented. We focus on the impact of missense changes, especially the c.2461A > C (p.Thr821Pro) variant and its association with late-onset LAMA2-MD. Finally, we report diagnostically challenging cases, highlighting the relevance of modern genetic analysis in the characterization of clinically heterogeneous muscle diseases.WileyRepositório do Centro Hospitalar Universitário de Lisboa Central, EPEOliveira, JGruber, ACardoso, MTaipa, RFineza, IGonçalves, ALaner, AWinder, TLSchroeder, JRath, JOliveira, MEVieira, ESousa, APVieira, JPLourenço, TAlmendra, LNegrão, LSantos, MMelo-Pires, MCoelho, Tden Dunnen, JTSantos, RSousa, M2020-08-10T14:43:46Z20182018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.17/3495engHum Mutat . 2018 Oct;39(10):1314-133710.1002/humu.23599info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-03-10T09:43:16Zoai:repositorio.chlc.min-saude.pt:10400.17/3495Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:20:48.418041Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
LAMA2 gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypes |
title |
LAMA2 gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypes |
spellingShingle |
LAMA2 gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypes Oliveira, J Alleles Biomarkers Brain Computational Biology Databases, Nucleic Acid Gene Frequency Genetic Variation Genotype Humans Immunohistochemistry Laminin Magnetic Resonance Imaging Muscular Dystrophies Genetic Association Studies Mutation Phenotype HDE GEN HDE NEU PED |
title_short |
LAMA2 gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypes |
title_full |
LAMA2 gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypes |
title_fullStr |
LAMA2 gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypes |
title_full_unstemmed |
LAMA2 gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypes |
title_sort |
LAMA2 gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypes |
author |
Oliveira, J |
author_facet |
Oliveira, J Gruber, A Cardoso, M Taipa, R Fineza, I Gonçalves, A Laner, A Winder, TL Schroeder, J Rath, J Oliveira, ME Vieira, E Sousa, AP Vieira, JP Lourenço, T Almendra, L Negrão, L Santos, M Melo-Pires, M Coelho, T den Dunnen, JT Santos, R Sousa, M |
author_role |
author |
author2 |
Gruber, A Cardoso, M Taipa, R Fineza, I Gonçalves, A Laner, A Winder, TL Schroeder, J Rath, J Oliveira, ME Vieira, E Sousa, AP Vieira, JP Lourenço, T Almendra, L Negrão, L Santos, M Melo-Pires, M Coelho, T den Dunnen, JT Santos, R Sousa, M |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório do Centro Hospitalar Universitário de Lisboa Central, EPE |
dc.contributor.author.fl_str_mv |
Oliveira, J Gruber, A Cardoso, M Taipa, R Fineza, I Gonçalves, A Laner, A Winder, TL Schroeder, J Rath, J Oliveira, ME Vieira, E Sousa, AP Vieira, JP Lourenço, T Almendra, L Negrão, L Santos, M Melo-Pires, M Coelho, T den Dunnen, JT Santos, R Sousa, M |
dc.subject.por.fl_str_mv |
Alleles Biomarkers Brain Computational Biology Databases, Nucleic Acid Gene Frequency Genetic Variation Genotype Humans Immunohistochemistry Laminin Magnetic Resonance Imaging Muscular Dystrophies Genetic Association Studies Mutation Phenotype HDE GEN HDE NEU PED |
topic |
Alleles Biomarkers Brain Computational Biology Databases, Nucleic Acid Gene Frequency Genetic Variation Genotype Humans Immunohistochemistry Laminin Magnetic Resonance Imaging Muscular Dystrophies Genetic Association Studies Mutation Phenotype HDE GEN HDE NEU PED |
description |
Congenital muscular dystrophy type 1A (MDC1A) is one of the main subtypes of early-onset muscle disease, caused by disease-associated variants in the laminin-α2 (LAMA2) gene. MDC1A usually presents as a severe neonatal hypotonia and failure to thrive. Muscle weakness compromises normal motor development, leading to the inability to sit unsupported or to walk independently. The phenotype associated with LAMA2 defects has been expanded to include milder and atypical cases, being now collectively known as LAMA2-related muscular dystrophies (LAMA2-MD). Through an international multicenter collaborative effort, 61 new LAMA2 disease-associated variants were identified in 86 patients, representing the largest number of patients and new disease-causing variants in a single report. The collaborative variant collection was supported by the LOVD-powered LAMA2 gene variant database (https://www.LOVD.nl/LAMA2), updated as part of this work. As of December 2017, the database contains 486 unique LAMA2 variants (309 disease-associated), obtained from direct submissions and literature reports. Database content was systematically reviewed and further insights concerning LAMA2-MD are presented. We focus on the impact of missense changes, especially the c.2461A > C (p.Thr821Pro) variant and its association with late-onset LAMA2-MD. Finally, we report diagnostically challenging cases, highlighting the relevance of modern genetic analysis in the characterization of clinically heterogeneous muscle diseases. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018 2018-01-01T00:00:00Z 2020-08-10T14:43:46Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.17/3495 |
url |
http://hdl.handle.net/10400.17/3495 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Hum Mutat . 2018 Oct;39(10):1314-1337 10.1002/humu.23599 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Wiley |
publisher.none.fl_str_mv |
Wiley |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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