P.8.1 Muscle biopsy findings in Limb Girdle muscle Dystrophy 2I (LGMD2I)

Abstract

To assess potential correlation of severity of Limb Girdle Muscular Dystrophy type 2I (LGMD2I) with morphological, immunohistochemical and immunoblot alterations, in muscle biopsies from 27 patients with (LGMD2I). Mutations in the FKRP (Fukutin Related Protein) gene produce a range of clinical phenotypes including Limb Girdle Muscular Dystrophy Type 2I (LGMD2I), which belong to the mild end of the clinical spectrum. Seven different FKRP mutations have been detected among Norwegian LGMD2I patients of whom the majority were homozygous for the common c.826C>A mutation, and presented with a milder phenotype. Muscle biopsies were obtained from 27 patients. Quantitative evaluation of morphological alterations in muscle cross- sections, and immunohistochemistry (IHC) with antibodies directed against the alpha-dystroglycan epitope, was performed by light microscopy. A semi-quantitative assessment of changes was recorded, point-graded and summarized as morphological sum-score for each biopsy. The following myopathic changes were graded in the scoring system: fibrosis, regeneration, atrophy, centralized nuclei, necrosis, and inflammation. Western blot (WB) analysis on muscle biopsy homogenates were carried with antibodies directed towards the core alpha-DG as well as the alpha-DG epitope. Muscle biopsies from 27 patients with LGMD2I presented large variation in morphological features (Table 1).