Résumé :
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Several different human diseases have been linked to mutations in the gene encoding lamin A/C (LMNA). Mutations in LMNA were first associated to autosomal forms of Emery-Dreifuss muscular dystrophy (EDMD), a rare slowly progressive humero-peroneal muscular dystrophy accompanied by early contractures and dilated cardiomyopathy with conduction defects. Since then LMNA mutations have been reported in several distinct phenotypes that affect skeletal and/or cardiac muscle, adipose tissue, peripheral nerve, bone, premature ageing or variable combination of these phenotypes. So far more than 350 different LMNA mutations have been identified in over 1700 subjects.The aim of our report is to communicate the first identified cases of laminopathy in Chile, two of which carry novel mutations.The first three cases presented in early childhood, with mild creatine kinase (CK) increase and delayed motor milestones. Electrophysiological assessment showed normal nerve conduction velocity with myopathic changes. Muscle histopathological studies showed unspecific dystrophic findings with normal immunostaining for dystrophin, merosine and other membrane proteins. Case 1 is a girl carrying a new de novo LMNA p.V442G mutation, manifesting as a myopathy during the first year of life, with neck and limb girdle muscle weakness of a scapulo-peroneal distribution. At 3 years of age, she presented increased motor difficulties; rigid spine syndrome and multiple limb retractions, pectus carinatum and mild restrictive respiratory involvement Case 2 is a girl that presented with a humero-peroneal myopathy beginning with lower limb weakness after 18 months of age. At the age of 8, she showed mild restrictive respiratory involvement, ventricular arrhythmia for which underwent a cardiac surgery to place a defibrillator. She and her mildly affected mother presented the LMNA p.Y259N mutation..Case 3 presented with a floppy infant syndrome, delayed motor milestones and pelvic girdle weakness since infancy. At the age of 20, he presents a typical Emery-Dreifuss syndrome associated with rigid spine as well as supraventricular arrhythmia. Molecular analysis showed a new de novo LMNA p.L245P mutation. Case 4 is a 41 years old woman that was followed due to a dilated myocardiopathy. She presented with progressive lower limb weakness associated with lypodystrophy. She carries the LMNA p.R541C mutation, which has never been reported associated before with features of lypodystrophy. JAB is supported by FONDECYT 1110159
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