[LS9-3A-2] Genetic Diagnosis of Spinal Muscular Atrophy in Japan
Spinal muscular atrophy (SMA) is a common neuromuscular disorder with an autosomal recessive inheritance trait. The severest form of SMA may be the leading genetic cause of infant death. In 1995, the survival of motor neuron gene (SMN) was identified in chromosome 5q13 as a candidate gene for SMA. SMN exists in two nearly identical copies, SMN1 and SMN2. SMN1 is absent from more than 95% of SMA patients and deleteriously mutated in the remaining patients. Thus, SMN1 has been recognized as an SMA-causing gene. On the other hand, SMN2 is now considered to be an SMA-modifying gene, because a high copy number of SMN2 can partially compensate for the lack of SMN1. Although SMA has long been considered an incurable disease, improved understanding of molecular mechanisms of SMN2 expression has spurred the development of therapeutic compounds indicating that we are now about to enter an era with the possibility that SMA can be treated. Thus, detection of the infants with SMN1-deletion and detailed SMN2 gene characterization will become more important. By foreseeing the future requirements, we have already established a rapid and accurate SMN1-deletion detection system, which may be applied to SMA screening. Screening policy varies country to country, but with effective treatment to cure or arrest the progression of SMA, newborn screening for the disease may be warranted in any country. In the present seminar, current status of SMA genetic diagnosis in Japan is reviewed and the future direction is discussed.