Objective: Spinal muscular atrophy (SMA) is an autosomal recessive disorder that results in symmetrical muscle weakness and wasting due to degeneration of the anterior horns of the spinal cord. The clinical picture of SMA is variable and childhood SMA has been classified into 3 types on the basis of the age of onset and clinical course. The survival motor neuron (SMN) gene was mapped to chromosome 5q13. The SMN1 gene has been recognized to be responsible for SMA because of homozygous deletions or intragenic mutations in SMN1 results in childhood onset of SMA. The main objective of this study was to determine the deletion frequency of SMN1 gene and to apply gene analysis in children patients with SMA.
Methods: The SMA patients were diagnosed and clinically typed according to the international diagnostic criteria, following up cases, and gene analysis. The PCR enzyme assay was used to detect the homozygous deletion of SMN1 gene in SMA patients. A dosage assay that combined multiplexed allele-specific PCR and DHPLC was used to determine the copy numbers of the SMN1 and SMN2 and detect SMN1 heterozygous deletion.
Results: (1) A total of 267 patients with SMA were diagnosed from 338 suspicious cases and 143, 82, and 42 cases were typed as types I, II, and III, with the percentages of 53.6% (143/267), 30.7% (82/267) and 15.7% (42/267), respectively. (2) Results of the present study showed that 68.5% (183/267) of SMA patients had homozygous deletions of exons 7 and 8 of SMN1 gene and 12.7% (34/267) had homozygous deletions of only exon 7 of SMN1 gene. The SMN1 heterozygous deletion was confirmed in 12.4% (33/267) of SMA patients. Non-deletion SMA patients accounted for 6.4%(17/267). The homozygous deletions of only exon 8 of SMN1 gene could not be detected. (3) The rates of homozygous or heterozygous deletion in types I and II were very similar. The rate of homozygous deletion was lower in type III than that in type I or II and rate of heterozygous deletion of type III was higher than that in types I or II.
Conclusion: (1) The frequency and pattern of deletions in the Chinese children patients with SMA are significantly different from that observed in Caucasians populations. Further gene characterization and subtle mutations within the SMN1 gene need to be studied in order to define the molecular basis of SMA in the Chinese population. (2) The gene diagnosis is a special and non invasive method as compared with other methods. A total of 80% patients can be diagnosed through the analysis of the homozygous deletion of SMN1 gene. (3) The clinical diagnosis and gene detection need to be studied in future for the SMA patients with type III.