Copy number analysis in a large-scale study of spinal muscular atrophy patients between two continuous generations in Iran

Abstract

Abstract Background:Spinal muscular atrophy (SMA) is a rare autosomal recessive inherited neuromuscular disease with about 1:6000 to 1:10,000 in newborns. Objectives:To evaluate the copy number variation of SMN1 and SMN2 genes between two generations, we experimented on 221 core families, including 221 patients and their parents (n=442). Materials & methods: Before sample collection, all cases were subjected to clinical diagnosis, electromyography, and nerve conduction velocity test. Moreover, DNA samples were analyzed by multiplex ligation-dependent probe amplification. Results: In this study, 92.7% of patients' SMN1 deletions were homozygous, whereas 7.3% of the SMN1 deletions were heterozygous. On the other hand, 92.9% of the parents had one copy of SMN1, and the remaining had two copies of SMN1. Since SMN2 has a disease-modifying role, accurate determination of SMN2 copy number can be helpful in the case of prognosis and genotype-phenotype correlation. The average SMN copies from parents represent the copy number in the parent's generation. Evaluations showed a negative correlation between the copy number of SMN1 and SMN2in children and their parents. Besides, when the average of SMN2 copy numbers was two in the parent's generation, 81% of the children were type I, and the rest were Type II/III. Also, in cases with three or more SMN2copy numbers in parents, approximately 90% of children were either type II or III. Conclusion: Accordingly, there is a possibility that the SMN2 copy numbers in parents could predict the disease severity in the next generation.