Résumé :
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Introduction Spinal muscular atrophy (SMA), the second most common lethal autosomal recessive disorder, has an incidence of 1/10,000 newborns. It is divided into acute Werdnig-Hoffmann disease (type I), intermediate form (type II), Kugelberg-Welander disease (type III) and adult form (type IV). The gene involved all four forms of SMA so called survival motor neuron (SMN) gene maps to chromosome 5q 11.2-13.3, is duplicated, with telomeric (tel SMN or SMN1) and centromeric copies (cent SMN or SMN2), Differencing with respect to their RNA expression patterns. SMN1 is hozygously deleted over 95 % of SMA patients. SMN2 may occur in more than two copies per diploid genome and its inactivation does not cause SMA. Previous studies showed that variation in the number of copies of the SMN2 gene contributes to the severity of SMA. In this study we examined deletions of the SMN1, SMN2, and NAIP genes in the SMA patients from the East of Algeria. Materials and methods Ninety two patients of Algerian origin, from 57 unrelated families were diagnosed as having SMA on the basis of clinical findings and electromyoneurography, All patients fulfilled the diagnostic criteria for proximal SMA defined by the International SMA Consortium and by Zerres et al. DNA from peripheral blood samples of the patients was extracted according to a standard technique. SMN exon 7 and 8 deletion analysis was performed by the PCR and enzyme-digestion method as described by van der Steege et al. All individuals were also tested for exons 4 and 5 deletion of NAIP gene. PCR conditions and primers used to amplify the exons 4 and 5 were identical to those of Roy et al. The SMN2 allele copies were determined by DNA-analysis using the Multiplex Ligation-dependent Probe Assay (MLPA) method Results There were 20 patients with type I SMA, 16 with type II SMA, 53 with type III SMA and 3 with type IV SMA. Homozygous deletions of SMN1 exons7and/or 8 were found in 75, 43 % of the families: 11/14 in type I, 7/10 in type II, 24/31 in type III and in type IV. Deletions of exon 4 and/or 5 of the NAIP gene were found in 4/14 of type I, 2/10 of type II and 9/31 of type III families. No correlation between deletions of one or both genes and phenotype severity was found. The quantitative analysis of SMN2 copies showed a significant correlation between SMN2 copy number and type of SMA. Thus, 73,33 % of patients with type I SMA carry one or two SMN2 copies and 58,33% of patients with type II SMA carry three SMN2 copies, whereas 96, 96 % of patients with type III SMA carry three or four SMN2 copies. Conclusion Phenotypic and genotypic analysis of Algerian patients with SMA approaches those observed in the other countries.
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