Résumé :
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Collagen VI-related muscle disorders, due to mutations in the 3 genes encoding Collagen VI, regroup Ullrich congenital muscular dystrophy, characterized by early onset generalized muscle weakness, marked proximal contractures and distal hyperlaxity, and Bethlem myopathy, a progressive myopathy, mostly proximal, with a moderate muscle weakness and contractures. Contractures are also prominent during early childhood in Emery-Dreifuss, muscular dystrophy caused by mutations in Lamin A/C gene (LMNA). We report here a family with symptoms overlapping between both COL VI related disorders and EDMD. The father and mother were clinically normal. Their two children (35 year-old daughter and 32 year-old son) showed similar type of clinical presentation but with a wide range in the clinical severity. For both, clinical symptoms appeared at 3 years of age, with progressive motor deficit and multiple retractions (axial and limbs -proximal and distal-). The evolution was markedly more severe for the son who was wheelchair-bound at 11 years. Muscle biopsies of the son and daughter performed at 13 and 25 years old, showed dystrophic changes and partial deficit in collagen VI immunostaining, with entirely or partially negative fibres. The father’s muscle biopsy showed similar findings but much more subtle. Studies on cultured skin fibroblasts also showed more pronounced collagen VI deficits in the children as compared to the father. Genetic studies revealed 2 different missense COL6A2 mutations in the father (p.Ala698Val in exon 26 affecting the C1 globular domain) and mother (p.Arg830Glu in exon 28 affecting the C2 globular domain), which were both transmitted to the children. Interestingly, the father and his daughter presented a new mutation in the LMNA gene (p.Gly523Arg). We hypothesize that the LMNA mutation could play a “protective” role in the daughter in regard of the COL6 mutations which could explain the difference in the clinical severity of the two children.
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