Résumé :
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Dysferlinopathies are autosomal recessive muscular dystrophies caused by mutations in the dysferlin (DYSF) gene that encodes for dysferlin (MIM 603009). Dysferlinopathy manifests as two main clinical phenotypes, distal Miyoshi’s myopathy and LGMD2B, however a wide range of clinical phenotypes --- ranging from sub-clinical to severe forms – may also be produced by similar mutations We are reporting the two first Chilean cases of dysferlinopathy with a molecular genetic analysis. A 26 year old man, from a consanguineous marriage, developed distal myopathy involving the posterior compartment of both legs. Impairment progressed in the in the lapse of three years to tights and the anterior compartment the right arm. CK levels at onset were 21237 UI/dl. Biopsy of the quadriceps showed unspecific dystrophic changes, and absent dysferlin immunostaining. In this patient, a novel one base-pair deletion of the exon 21 was identified (c.1948delC) at a homozygous state. This leads to a shift of the reading-frame resulting in a premature termination codon (p.Leu650TyrfsX6). The second case is a 26 year old woman that developed a progressive weakness in her right leg. Examination showed an asymmetrical atrophy of the calves and both anterior recti. Normal walking was impaired, but other muscular groups were less affected. CK levels at onset were 8870 UI/dl. Biopsy of the quadriceps showed minimal dystrophic changes, dysferlin immunostaining was absent. Two disease-causing mutations, at a compound heterozygous state, were detected in her: a frame shifting mutation of the exon 27 (c.2858dupT, p.Phe954ValfsX2) and a novel missense mutation of the exon 13 (c.1276G>A, p.Gly426Arg). The latter, was not retrieved in 200 control chromosomes and affects a highly conserved amino-acid residue located in C2 domain C of dysferlin. We conclude that this novel missense change is pathogenic Further studies to typify dysferlinopathy in the region will contribute of this dystrophy.
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