Comparison of dysferlin expression in human skeletal muscle with that in monocytes for the diagnosis of dysferlin myopathy

Background: Dysferlinopathies are caused by mutations in the dysferlin gene (DYSF). Diagnosis is complex due to the high clinical variability of the disease and because dysferlin expression in the muscle biopsy may be secondarily reduced due to a primary defect in some other gene. Dysferlin is also...

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Detalles Bibliográficos
Autores: Gallardo E., de Luna N., Diaz-Manera J., Rojas-García R., Gonzalez-Quereda L., Flix B., de Morrée A., van der Maarel S., Illa I.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2011
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p11610
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11610
https://www.scopus.com/inward/record.uri?eid=2-s2.0-83455262487&doi=10.1371%2fjournal.pone.0029061&partnerID=40&md5=f5c17765ff3c74c1c1ba4164132f92df
Access Level:acceso abierto
Palabra clave:dysferlin
CD14 antigen
DYSF protein, human
membrane protein
muscle protein
adolescent
adult
aged
article
child
clinical article
controlled study
dysferlin gene
dysferlin myopathy
female
gene
gene expression
gene mutation
human
human cell
human tissue
immunohistochemistry
male
monocyte
muscle biopsy
mutational analysis
myopathy
preschool child
protein expression
skeletal muscle
Western blotting
biopsy
comparative study
dysferlinopathy
genetics
limb girdle muscular dystrophy
metabolism
mutation
nucleotide sequence
pathology
solubility
Adult
Antigens, CD14
Biopsy
DNA Mutational Analysis
Female
Humans
Male
Membrane Proteins
Monocytes
Muscle Proteins
Muscle, Skeletal
Muscular Dystrophies, Limb-Girdle
Mutation
Solubility
Descripción
Sumario:Background: Dysferlinopathies are caused by mutations in the dysferlin gene (DYSF). Diagnosis is complex due to the high clinical variability of the disease and because dysferlin expression in the muscle biopsy may be secondarily reduced due to a primary defect in some other gene. Dysferlin is also expressed in peripheral blood monocytes (PBM). Studying dysferlin in monocytes is used for the diagnosis of dysferlin myopathies. The aim of the study was to determine whether dysferlin expression in PBM correlates with that in skeletal muscle. Methodology/Principal Findings: Using western-blot (WB) we quantified dysferlin expression in PBM from 21 pathological controls with other myopathies in whom mutations in DYSF were excluded and from 17 patients who had dysferlinopathy and two mutations in DYSF. Results were compared with protein expression in muscle by WB and immunohistochemistry (IH). We found a good correlation between skeletal muscle and monocytes using WB. However, IH results were misleading because abnormal expression of dysferlin was also observed in 13/21 pathological controls. Conclusions/Significance: The analysis of dysferlin protein expression in PBM is helpful when: 1) the skeletal muscle IH pattern is abnormal or 2) when muscle WB can not be performed either because muscle sample is lacking or insufficient or because the muscle biopsy is taken from a muscle at an end-stage and it mainly consists of fat and fibrotic tissue. © 2011 Gallardo et al.