Abstract

MOLECULAR ANALYSIS OF THE PROMOTER REGION OF THE SMN2 GENE IN PATIENTS OF SPINAL MUSCULAR ATROPHY TOWARDS SCRUTINIZING THE CLINICAL SEVERITY OF SPINAL MUSCULAR ATROPHY

, Atif AB*, Chan YY, Shamim A K, Gotam K, Zilfalil BA

Abstract

In patients of spinal muscular atrophy from different clinical types and with different copy numbers of the SMN2 gene the level of FL- SMN (Full length Survival of Motor Neuron) protein is reported to be same and even with same copy no. of the SMN2 gene the FL-SMN levels were reported to be different. We postulated that the difference in the promoter region of SMN2 gene might produce the different level of FL-SMN protein in SMA patients. To verify this hypothesis, the DNA samples of 69 SMA patients were analyzed forSMN1 deletion followed by the SMN2 copy no. analysis and NAIP deletion analysis to remove any clinical bias. Based on the bioinformatics analysis and the designed primers, PCR amplification was done for different regions in promoter of the SMN2 gene in SMA patients (n=10) followed by direct DNA sequencing. The molecular analysis confirmed the absence of any variation in the promoter region of the SMN2 gene between normal healthy individuals (n=2) and SMA patients. To the best of our knowledge, this is first study analyzing the promoter region of SMN2 gene in all clinical types of SMA.

Keywords: SMA, Promoter, SMN2 gene, spinal muscular atrophy.