Spinal muscular atrophy (SMA) is one of the most common autosomal recessive disorders, characterized by degeneration of anterior horn cells in the spinal cord, and leads to progressive muscular weakness and atrophy. SMA is clinically divided into four subtypes depending on age at onset and clinical course. Genetic linkage studies have mapped responsible genes for all clinical types of SMA to chromosome 5q13, homozygous deletion in SMN1 gene causes the disease but the clinical severity may be modified by copy number of homologous gene SMN2 as well as the extent of deletion at the SMN locus. In the present study, to elucidate the correlation between genotype and clinical severity in SMA patients, we analyzed the molecular genetics features of 92 Algerian patients with SMA, from 57 unrelated families. All patients fulfilled the diagnostic criteria of SMA as defined by the International SMA Consortium. Genomic DNA was extracted from peripheral blood following the conventional procedures. Deletions of exons 7 and 8 of the SMN gene were analyzed by an enzyme digestion assay. NAIP gene analysis was performed by PCR amplification of exon 4 and 5. SMN2 gene copy number analysis was carried out by the use of a quantitative PCR-based assay. Patients were classified into type I SMA (20 patients), type II (16 patients), Type III (53 patients) and type IV (3 patients). 43 of the 57 SMA families (75.43%) were homozygous for SMN1 deletion of exon7 and 8 (type I, type II, type III and type IV). NAIP exon 4 and 5 were deleted in 15 (4/14 type I, 2/10 type II, 9/31 type III, 0 type IV), of 57 SMA families. In all patients with a NAIP deletion of exon 4 and 5, there was also a SMN1 deletion of exon 7. Frequency of NAIP deletions were significantly higher in type I patients than in type II or III patients. Also SMN2 copy numbers were higher in SMA type IV and type III than in type I and type II. This increase in copy number of SMN2 gene may be responsible for the less severe form of SMA with late onset of symptoms. Our results are compatible with the data of the literature.

Username
Password