Résumé :
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The most frequent form of axonal autosomal recessive Charcot-Marie-Tooth neuropathy is a laminopathy. R289C is the only mutation descried so far in all reported families. This is a phenotype study of patients with R289C mutation in Lamin A/C gene. Fifteen patients belonging to 5 Moroccan consanguineous families were examined clinically and electrophysiologically. In one patient, a peroneal nerve biopsy was performed. Linkage to 1q21.2 was then demonstrated and a mutation in the coding region of the lamin A/C gene was identified by direct sequencing. Mean age at onset was 14.6 ± 3.8 years (range: 8 to 20 years). Most of the cases had the common CMT clinical phenotype. Four patients, with the longest disease duration, had pronounced atrophy and weakness of scapular muscles. The severity was variable even in the same family. The electrophysiological findings were consistent with axonal form of CMT. The mean MNCV was 53.5 ± 7.6 m/s (range: 36 to 66) for median nerve. The CMAP amplitudes in upper limbs were either reduced (in 5 patients) or normal (in 9 patients). Sensory responses were abolished in most of patients for both upper and lower limbs. Needle electromyography showed neurogenic pattern in both distal and proximal muscles predominantly in lower limbs. Morphological finding showed axonal neuropathy. R289C mutation in the lamin A/C gene was identified in all families The main phenotype chracteristics of CMT with Lamin A/C mutations are: onset during the last teens or the second decade, impairment of proximal muscles, the variability of functional disability even within the same family and the axonal disorder process. This form is described mostly in North Africa and is due to the same mutation suggesting a probable founder effect.
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