quantitative analysis of smn1 gene and estimation of smn1 deletion carrier frequency in iranian population based on real-time pcr

spinal muscular atrophy (sma) is a common autosomal recessive neuromuscular disorder caused by the loss of α-motor neurons in the spinal cord. the survival motor neuron (smn) protein is encoded by 2 genes, smn1 and smn2. the most frequent mutation is the biallelic deletion of exon 7 of the smn1 gene. smn2 cannot compensate for the loss of smn1, due to the exclusion of exon 7. carrier frequency studies of sma have been reported for various populations. the aim of our study was to estimate the frequency of the smn1 exon 7 deletion in our population as well as reporting our carrier detection for the families with a history of sma and prenatal diagnosis for these families over the last 10 years. we continued detecting exon 7 deletion of the smn1 gene for the affected patients and fetuses suspected to have sma by a semi-quantitative method up to two years ago. then, this method was replaced in our center by a more reliable and highly sensitive quantitative real-time pcr assay with sybr green dye which detects the copy number of the smn1 gene. more recently, we applied the mlpa technique for determining copy number in smn2 gene. the carrier frequency of sma in 200 healthy unrelated, non-consanguineous couples from different parts of iran was also assessed by real time pcr analysis. according to the international sma diagnostic criteria, 195 out of 243 families were classified as sma type i, 30 as type ii, and 18 as type iii. the analysis of exon 7 deletion among living affected children showed that 94% of the patients with sma type i, 95% with type ii families and 100% with type iii had homozygous deletions of smn1 gene. according to the results of prenatal diagnosis, 21 out of 92 fetuses (22.8%) were found to be affected and these pregnancies were terminated. the homozygosity frequency for the deletion of smn1 exon 7 for all 3 types was 94%, similar to those of western europe, china, japan and kuwait. the carrier frequency for the smn1 exon 7 deletion in our population was determined to be 1 in 20 iranians. our data showed that the sma carrier frequency in iran was higher than european population and further screening programs for carrier detection and prenatal testing should be implemented.