Résumé :
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Communication n° 578 Spinal muscular atrophies (SMA) are characterized by progressive anterior horn cell degeneration, leading to motor weakness, muscular atrophy and denervation. Numerous SMA phenotypes have been reported, differing by the distribution of paralysis, the age at onset and the mode of inheritance. Here we report on a phenotype of autosomal dominant SMA in a large European pedigree, characterized by childhood onset and benign evolution. In all of patients, motor milestones were normally acquired, except walking ability which was delayed in the majority of cases. Weakness of the pelvic girdle muscles was the main symptom, causing disability to run and to climb stairs. Physical examination showed a symmetrical atrophy of the thigh and leg muscles contrasting with normal or slightly weak scapular girdle muscles. Axial and distal muscles strength was normal. No chest deformity was noted, scoliosis was absent and patients were still ambulant at adulte age. Surprisingly, osteotendinous reflexes were preserved and/or brisk in the lower and upper limbs but there was no pyramidal sign. Diagnosis of motor neuron disease was suspected on neurological assays, showing muscle denervation with normal motor and sensory nerve conduction velocities. Muscle biopsy showed a pattern of denervation. Homozygous SMN gene deletion was not found in the DNA of probants. We performed genetic analysis in this pedigree by whole genome scanning. Studying DNA of the affected individuals only, we identified a common haplotype in the 14q32.3 region located between loci D14S973 and D14S1007, cosegregating with the disease. (Zmax: 3,85 at ?=0.00). This interval corresponds to a large physical distance of 13 megabases according to the electronic databases. Recruitment and genetic analysis of other cases of autosomal dominant SMA would be very helpful to narrow the critical region. Testing candidate genes in this region will probably allow identifying a new gene involved in motor neuron degeneration.
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