Résumé :
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Communication n° 568 Introduction Mutations in LMNA encoding Lamins A/C are responsible of several disorders named laminopathies involving striated muscles as well as adipose, nervous, cutaneous and skeletal tissues. Mutations in FACE1, encoding a metalloproteinase specifically involved in the post-translational processing of Lamin A precursor, are associated to a severe progeroid syndrome called Restrictive Dermopathy, a lethal progeroid syndrome and Mandibuloacral Dysplasia. Objectives To report the clinical and genetic features of a patient with congenital myopathy, arthrogryposis and progeroid features carrying a novel FACE1 mutation. Methods The medical and histological data of a 28 years old female patient was systematically reviewed. LMNA and FACE1 genes were screened. Skin fibroblasts and myoblasts were investigated by immunoflurescence and western Blot methods. Results The patient showed a combination of several clinical features: muscle weakness with fibre type disproportion on muscle biopsy together with restrictive respiratory failure, arthrogryposis and progeroid features including short stature, retrognathism, thin and sclerodermiform skin, abnormal clavicles, distal acro-osteolysis, osteoporosis and sparse hairs, generalized calcinosis, renal artery compression, hypertension, albuminuria, hypertriglyceridemia and hypercholesterolemia, hepatic steatosis with hepatomegaly. No LMNA mutation was found while we identified a homozygous FACE1 mutation: c.275T>C, predicted to cause a p.Leu94Pro substitution at the protein level. Immunoflurescence and western Blot analyses are in progress to further dissect the pathomechanisms underlying this novel FACE1 mutation. Conclusion This is the first report of a complex progeroid phenotype including myopathic features due to homozygous FACE1 mutations, thus extending the clinical spectrum of diseases associated to FACE1 mutation. These results indicate that skeletal muscle can also be affected by the perturbation of Lamins A/C processing pathway.
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