These results identify critical domains within the SMN protein and have an impact on our understanding of the SMN protein with regards to SMA as well as cellular biology.
A deficiency of the SMN protein results in the inherited neurodegenerative condition SMA (spinal muscular atrophy), a leading cause of infant mortality specifically affecting spinal motor neurons.
Infantile spinal muscular atrophy (SMA) caused by homozygous SMN1 gene deletions/mutations is characterized by neuronal loss and axonopathy of motor neurons.
Of the 12 neuromuscular studies exclusively on spinal muscular atrophy type 1 (SMA1), six (50%) reported decreased hospitalizations and nine (75%) reported on mortality outcomes.
Linkage studies, as well as the analysis of the SMN gene, recognised that SMA variants (with severe arthogryposis or cerebellar or diaphragmatic involvement) are not linked to chromosome 5q markers.
Deletion or mutation of SMN1 coupled with the inability of SMN2 to compensate for the loss of SMN1 due to exon 7 skipping causes spinal muscular atrophy (SMA), one of the leading genetic diseases of children.
In contrast to other neurodegenerative disorders, SMA is a genetically homozygous autosomal recessive disease that is caused by deficiency of the survival motor neuron (SMN) protein.
The assay has been optimized and tested in 48 healthy controls, 20 known patients with SMA, 12 carriers (one SMN1 copy), and 8 amniotic fluids suspected of having SMA for whom we had determined the SMN1/SMN2 deletion by an additional PCR-RFLP method.
Importantly, an SMA-causing mutation in the Tudor domain of SMN completely abolished translational repression, a strong indication for the functional significance of this novel SMN activity in the pathology.
Our research elucidated the genetic load and SMN gene variants that are present in the Chinese population, and could serve as the basis for a nationwide program of genetic counseling and clinical/prenatal diagnosis to prevent SMA in China.
Spinal muscular atrophy (SMA) is a rare autosomal recessive neuromuscular disorder most commonly caused by a deletion or mutation in the survival motor neuron 1 (SMN1) gene, which leads to insufficient levels of survival motor neuron (SMN) protein.
Spinal Muscular Atrophy (SMA) is a neuromuscular disease caused by mutations in the Survival Motor Neuron 1 gene, resulting in very low levels of functional Survival of Motor Neuron (SMN) protein.
Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality worldwide, is characterised by the homozygous loss of the survival motor neuron 1 (SMN1) gene.
The primary cause of most, if not all, forms of childhood-onset spinal muscular atrophy appears to be the homozygous loss of the telomeric copy of the survival motor neuron (SMNT) gene.
These findings demonstrate how rare variants influence pre-mRNA splicing of SMN and reveal the functional influence of c.863G>T (r.835_*3del, p.Gly279Glufs*5) variant in patients with SMA.
In addition, analysis of cloned DNA segments from within the SMA candidate region has identified the presence of a novel, chromosome 5-specific, low copy repeated sequence which is distributed throughout the region containing the SMA gene as well as in at least four other regions of chromosome 5.