OBJECTIVE To investigate the potential association of plastin 3 (PLS3) expression levels in the blood with disease severity in spinal muscular atrophy (SMA). DESIGN Measurement of PLS3 messenger RNA levels in the blood of patients with types I, II, and III SMA. SETTING Pediatric Neuromuscular Clinical Research Network SMA Natural History study. PARTICIPANTS A cohort of 88 patients of both...

Here we report the case of an ALS patient found to carry both a novel heterozygous change (c.194G>A) within the spastin gene and a homozygous deletion of the SMN2 gene. The patient was started on valproic acid (VPA, 600 mg/die per os) considering the capacity of this drug of increasing survival motor neuron through an epigenetic mechanism. Patient clinical course and molecular effects of VPA on...

A disease of actin transport? pinal muscular atrophy (SMA), a motoneuron disease that results in paralysis and death usually before age 3, is caused by loss of the SMN1 gene. But what does the established splicing function of SMN1 have to do with motoneurons? Perhaps very little, say Rossoll et al., who on page 801 show that SMN1 is part of a complex that drags ␤-actin mRNA out to growth cones ...

Spinal muscular atrophy (SMA) is a motor neuron degenerative disease caused by low levels of the survival motor neuron (SMN) protein and is linked to mutations or loss of SMN1 and retention of SMN2. How low levels of SMN cause SMA is unclear. SMN functions in small nuclear ribonucleoprotein (snRNP) biogenesis, but recent studies indicate that SMN may also function in axons. We showed previously...

A disease of actin transport? pinal muscular atrophy (SMA), a motoneuron disease that results in paralysis and death usually before age 3, is caused by loss of the SMN1 gene. But what does the established splicing function of SMN1 have to do with motoneurons? Perhaps very little, say Rossoll et al., who on page 801 show that SMN1 is part of a complex that drags ␤-actin mRNA out to growth cones ...

Spinal muscular atrophy (SMA) describes a group of disorders associated with spinal motor neuron loss. In this review we provide an update regarding the most common form of SMA, proximal or 5q-SMA, and discuss the contemporary approach to diagnosis and treatment. Electromyography and muscle biopsy features of denervation were once the basis for diagnosis, but molecular testing for homozygous de...

Mutations in the SMN1 (survival motor neuron 1) gene cause spinal muscular atrophy (SMA). We now show that SMN protein, the SMN1 gene product, interacts directly with the tumor suppressor protein, p53. Pathogenic missense mutations in SMN reduce both self-association and p53 binding by SMN, and the extent of the reductions correlate with disease severity. The inactive, truncated form of SMN pro...

Modified U1 snRNAs bound to intronic sequences downstream of the 5' splice site correct exon skipping caused by different types of mutations. Here we evaluate the therapeutic activity and structural requirements of these exon-specific U1 snRNA (ExSpeU1) particles. In a severe spinal muscular atrophy, mouse model, ExSpeU1, introduced by germline transgenesis, increases SMN2 exon 7 inclusion, SMN...

A disease of actin transport? pinal muscular atrophy (SMA), a motoneuron disease that results in paralysis and death usually before age 3, is caused by loss of the SMN1 gene. But what does the established splicing function of SMN1 have to do with motoneurons? Perhaps very little, say Rossoll et al., who on page 801 show that SMN1 is part of a complex that drags ␤-actin mRNA out to growth cones ...