Spinal muscular atrophy genetics

Editors-in-Chief: C. Michael Gibson, M.S., M.D.; Priyamvada Singh, MBBS

Overview
Spinal muscular atrophy is caused by mutation in SMN (survival motor neuron) gene present on chromosome 5q 13 in 98.6% of patients. The chromosome 5 contains an inverted duplication that contains the SMN1 gene (this is mutated in patients with SMA) and the SMN2 gene (a duplication of SMN1 that differs from it by only five nucleotides). Due to this difference in nucleotide in SMN2 gene, a truncated (Survival motor neuron) SMN protein is produced, much of which is non-functional and thus degraded. However, some of the SMN2 gene skips this and are able to produce some functional protein. The number of copies of SMN2 per chromosome 5 and the amount of SMN protein are inversely correlated with the severity of disease. 95% of patients of SMA with SMA have deletions of the SMN1 gene whereas others have intragenic, denovo mutation or gene conversion.