Abstract
BackgroundDysferlinopathies 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 FindingsUsing 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/SignificanceThe 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.
Highlights
Dysferlinopathy is a type of muscular dystrophy characterized by mutations in the dysferlin gene (DYSF) gene [1,2]
When a control antibody against b-amyloid was used we observed the dysferlin doublet only in the non-bound fraction (Figure 1C). These results indicate that both bands correspond to dysferlin protein and support using both of them to quantify dysferlin in peripheral blood monocytes (PBM)
Our study showed a reproducible relationship between dysferlin expression in skeletal muscle and in PBM by western blot (WB) analysis
Summary
Dysferlinopathy is a type of muscular dystrophy characterized by mutations in the DYSF gene [1,2]. As well as in skeletal muscle, dysferlin is expressed in peripheral blood CD14+ monocytes (PBM), as reported in a series of 12 patients with MM or LGMD2B [12]. The findings from this latter study suggested that studying the expression of dysferlin protein in these more accessible cells could be a reliable method to diagnose dysferlinopathies and a valid alternative to muscle biopsy. We analysed a large series of genetically characterized patients comparing the expression of dysferlin in skeletal muscle by immunohistochemistry (IH) and western blot (WB) with that in PBM. The aim of the study was to determine whether dysferlin expression in PBM correlates with that in skeletal muscle
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