Résumé :
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A child presenting with hypotonia and muscle weakness since infancy, ambulation until twelve years of age, seizures and normal cognitive function is described. CK was elevated (650-1420 IU/L). Brain MRI showed a few abnormal T2 white matter changes. Muscle biopsy showed dystrophic features and skin biopsy demonstrated absence of merosin immunostaining (300 kd antibodies, Novocastra Laboratories). Molecular genetic studies detected heterozygote mutations in both the LAMA2 (Val1754X) and FKRP (A114G ) genes, which were traced to the father and to the mother respectively. Two subsequent sibling fetuses carried the LAMA2 mutation. In one of them the FKRP mutation was also detected in one allele and in the other the FKRP gene was normal at both alleles. Even though the genotype of the two aborted fetuses and the patient were identical at the LAMA2 locus, the fetuses had normal merosin staining in chorionic villus sampling, whereas the patient was merosin-negative. Our findings suggest an additional potential interactive mechanism to LAMA2, possibly of the FKRP protein which is essential for preserving the sarcolemma integrity. These results suggest that merosin-defficiency may be the result of di-genic inheritance
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