神经科医生：临床与治疗杂志

抽象的

Genetics of Spinal Muscular Atrophy and Splicing of Smn Gene

Ashraf A Nazir S, Murtaza M, Imtiaz MU, Sohail S*, Nisar M, Abbas S, Farooq M, Sohail F and Rana H

Spinal muscular atrophy is characterized by loss of motor neurons and muscle atrophy, largely in childhood. It is a devastating neuromuscular disorder. In humans, nearly two identical inverted SMN genes (SMN1, SMN2) are present on chromosome 5q13. Homologous deletion of SMN1 results in SMA.SMA is initiated by low levels of the survival motor neuron protein (SMN) because of inactivating mutations in the encoding gene SMN1. Another functional protein for survival is produced by second duplicate gene SMN2.It produces a shortened, unstable SMN messenger RNA. From alternative splicing it produces a small length fully functional SMN messenger RNA. For SMA clinical severity, SMN2 gene copy number is a good prognostic biomarker. Many therapeutical strategies for spinal muscular atrophy are in clinical trials. Recently, Antisense oligonucleotide (ASO) therapy has been licensed. Though, several factors recommend that complementary strategies may be desirable for the long-term maintenance of neuromuscular disorder. During the establishment of structural connections of neuromuscular system, SMN protein is required in highest amount. Besides, people receiving SMN-based treatments may be vulnerable to delayed symptoms if rescue of the neuromuscular system is incomplete. Hence, for the treatment of CNS and periphery, a comprehensive whole-lifespan approach to SMA therapy is required. This therapy includes both SMN-dependent and SMN-independent strategies for the enhancement of SMN expressions many current and planned clinical trials are designed.