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dc.contributor.authorAlhamidi, Maisoon
dc.contributor.authorBrox, Vigdis
dc.contributor.authorStensland, Eva
dc.contributor.authorLiset, Merete
dc.contributor.authorLindal, Sigurd
dc.contributor.authorNilssen, Øivind
dc.date.accessioned2018-06-27T07:14:58Z
dc.date.available2018-06-27T07:14:58Z
dc.date.issued2017-07
dc.description.abstract<p>Limb girdle muscular dystrophy type 2I (LGMD2I) is a progressive disorder caused by mutations in the FuKutin-Related Protein gene (FKRP). LGMD2I displays clinical heterogeneity with onset of severe symptoms in early childhood to mild calf and thigh hypertrophy in the second or third decade. Patients homozygous for the common FKRP mutation c.826C>A (p.Leu276Ile) show phenotypes within the milder end of the clinical spectrum. However, this group also manifests substantial clinical variability.</p> FKRP deficiency causes hypoglycosylation of α-dystroglycan; a component of the dystrophin associated glycoprotein complex. α-Dystroglycan hypoglycosylation is associated with loss of interaction with laminin α2, which in turn results in laminin α2 depletion. Here, we have attempted to clarify if the clinical variability seen in patients homozygous for c.826C>A is related to alterations in muscle fibre pathology, α-DG glycosylation levels, levels of laminin α2 as well as the capacity of α-DG to bind to laminin. We have assessed vastus lateralis muscle biopsies from 25 LGMD2I patients harbouring the c.826C>A/c.826C>A genotype by histological examination, immunohistochemistry and immunoblotting. No clear correlation was found between clinical severity, as determined by self-reported walking function, and the above features, suggesting that more complex molecular processes are contributing to the progression of disease.en_US
dc.description.sponsorshipHelse Nord (MA, ØN)en_US
dc.descriptionAccepted manuscript version. Published version available at <a href=https://doi.org/10.1016/j.nmd.2017.02.015> https://doi.org/10.1016/j.nmd.2017.02.015 </a>.en_US
dc.identifier.citationAlhamidi, M., Brox, V., Stensland, E., Liset, M., Lindal, S. & Nilssen, Ø. (2017). Limb girdle muscular dystrophy type 2I: No correlation between clinical severity, histopathology and glycosylated α-dystroglycan levels in patients homozygous for common FKRP mutation. Neuromuscular Disorders, 27(7), 619-626. https://doi.org/10.1016/j.nmd.2017.02.015en_US
dc.identifier.cristinIDFRIDAID 1501463
dc.identifier.doi10.1016/j.nmd.2017.02.015
dc.identifier.issn0960-8966
dc.identifier.issn1873-2364
dc.identifier.urihttps://hdl.handle.net/10037/13012
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalNeuromuscular Disorders
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750en_US
dc.subjectLimb Girdle Muscular Dystrophyen_US
dc.subjectFKRPen_US
dc.subjectdystroglycanen_US
dc.subjectlaminin α2en_US
dc.titleLimb girdle muscular dystrophy type 2I: No correlation between clinical severity, histopathology and glycosylated α-dystroglycan levels in patients homozygous for common FKRP mutationen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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