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LAMA2 gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypes

2018Journal article Open access
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dc.contributor.authorOliveira, J
dc.contributor.authorGruber, A
dc.contributor.authorCardoso, M
dc.contributor.authorTaipa, R
dc.contributor.authorFineza, I
dc.contributor.authorGonçalves, A
dc.contributor.authorLaner, A
dc.contributor.authorWinder, TL
dc.contributor.authorSchroeder, J
dc.contributor.authorRath, J
dc.contributor.authorOliveira, ME
dc.contributor.authorVieira, E
dc.contributor.authorSousa, AP
dc.contributor.authorVieira, JP
dc.contributor.authorLourenço, T
dc.contributor.authorAlmendra, L
dc.contributor.authorNegrão, L
dc.contributor.authorSantos, M
dc.contributor.authorMelo-Pires, M
dc.contributor.authorCoelho, T
dc.contributor.authorden Dunnen, JT
dc.contributor.authorSantos, R
dc.contributor.authorSousa, M
dc.date.accessioned2020-08-10T14:43:46Z
dc.date.available2020-08-10T14:43:46Z
dc.date.issued2018
dc.description.abstractCongenital 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationHum Mutat . 2018 Oct;39(10):1314-1337pt_PT
dc.identifier.doi10.1002/humu.23599pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/3495
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.subjectAllelespt_PT
dc.subjectBiomarkerspt_PT
dc.subjectBrainpt_PT
dc.subjectComputational Biologypt_PT
dc.subjectDatabases, Nucleic Acidpt_PT
dc.subjectGene Frequencypt_PT
dc.subjectGenetic Variationpt_PT
dc.subjectGenotypept_PT
dc.subjectHumanspt_PT
dc.subjectImmunohistochemistrypt_PT
dc.subjectLamininpt_PT
dc.subjectMagnetic Resonance Imagingpt_PT
dc.subjectMuscular Dystrophiespt_PT
dc.subjectGenetic Association Studiespt_PT
dc.subjectMutationpt_PT
dc.subjectPhenotypept_PT
dc.subjectHDE GENpt_PT
dc.subjectHDE NEU PEDpt_PT
dc.titleLAMA2 gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1337pt_PT
oaire.citation.issue10pt_PT
oaire.citation.startPage1314pt_PT
oaire.citation.titleHuman mutationpt_PT
oaire.citation.volume39pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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