|
Spinal Muscular Atrophy
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
After nusinersen was found to increase levels of SMN protein in the CNS of mice and subhuman primates without causing significant adverse events, it was advanced into clinical studies in patients with SMA.
|
28799578 |
2017 |
|
Spinal Muscular Atrophy
|
0.700 |
Biomarker
|
disease |
BEFREE |
While a number of experimental therapeutics have targeted the ISS-N1 element of SMN2 pre-mRNA, the development of E1 ASOs provides a new molecular target for SMA therapeutics that dramatically extends survival in two important pre-clinical models of disease.
|
24781211 |
2014 |
|
Spinal Muscular Atrophy
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
The abrogation of the SF2/ASF-dependent ESE is the basis for inefficient inclusion of exon 7 in SMN2, resulting in the spinal muscular atrophy phenotype.
|
11925564 |
2002 |
|
Spinal Muscular Atrophy
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Seven index patients being not deleted for the SMN gene who belonged to a well-defined SMA plus variant that has already been shown to be unlinked with chromosome 5q markers: diaphragmatic SMA, SMA plus olivopontocerebellar hypoplasia, SMA with congenital arthrogryposis and bone fractures.2.
|
8677029 |
1996 |
|
Spinal Muscular Atrophy
|
0.700 |
Biomarker
|
disease |
BEFREE |
However, the molecular pathway linking SMN defect to the SMA phenotype remains unclear.
|
20225030 |
2009 |
|
Spinal Muscular Atrophy
|
0.700 |
Biomarker
|
disease |
BEFREE |
These studies provide the first characterization of the porcine SMN1 gene and SMN protein and suggest that a transgenic swine SMA model is feasible.
|
18651653 |
2008 |
|
Spinal Muscular Atrophy
|
0.700 |
Biomarker
|
disease |
BEFREE |
These findings identify SAM68 as the first physiological regulator of SMN2 splicing in an SMA mouse model.
|
26438828 |
2015 |
|
Spinal Muscular Atrophy
|
0.700 |
Biomarker
|
disease |
BEFREE |
This paper illustrates the broad clinical and genetic spectrum of SMA and includes reports of MLPA results and clinical descriptions of a patient with homozygous absence of SMN1 and only one SMN2 (prenatal onset SMA type 1), an asymptomatic woman with five SMN2 (lacking SMN1) and representative patients with SMA types 1, 2 and 3.
|
17049859 |
2006 |
|
Spinal Muscular Atrophy
|
0.700 |
Biomarker
|
disease |
BEFREE |
SMN gene dosage analyses, which can determine the copy numbers of SMN1 and SMN2 (an SMN1 homolog and a modifier for SMA), have been developed for SMA carrier testing and to confirm that SMN1 is heterozygously absent in symptomatic individuals who do not lack both copies of SMN1.
|
12436240 |
2002 |
|
Spinal Muscular Atrophy
|
0.700 |
Biomarker
|
disease |
BEFREE |
To clarify the relationship between SMN2 and the disease severity of SMA, we performed fluorescence-based quantitative polymerase chain reaction assay of the copy number of SMN2 in 27 patients (11 type I and 16 type II-III) homozygous for SMN1 deletion.
|
12242541 |
2002 |
|
Spinal Muscular Atrophy
|
0.700 |
Biomarker
|
disease |
BEFREE |
Genotype-phenotype correlation allowed inference of the effect of each mutation on the function of the SMN1 protein and the role of the SMN2 copy number in modulating the SMA phenotype.
|
10205265 |
1999 |
|
Spinal Muscular Atrophy
|
0.700 |
Biomarker
|
disease |
BEFREE |
We show that aclarubicin effectively induces incorporation of exon 7 into SMN2 transcripts from the endogenous gene in type I SMA fibroblasts as well as into transcripts from a SMN2 minigene in the motor neuron cell line NSC34.
|
11734549 |
2001 |
|
Spinal Muscular Atrophy
|
0.700 |
Biomarker
|
disease |
BEFREE |
We have recently shown that ICV delivery of scAAV9-SMN is more effective than a similar dose of vector administered via an IV injection, thereby providing an important mechanism to examine a timeline for rescuing the disease and determining the therapeutic window in a severe model of SMA.
|
24722206 |
2014 |
|
Spinal Muscular Atrophy
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein, whose role in pathogenesis remains unclear.
|
29069603 |
2017 |
|
Spinal Muscular Atrophy
|
0.700 |
Biomarker
|
disease |
BEFREE |
Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2.
|
11839954 |
2002 |
|
Spinal Muscular Atrophy
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
We sought to evaluate whether hypoxia was capable of altering SMN2 exon 7 splicing and whether increased oxygenation could modulate disease in a severe SMA mouse model.
|
22763238 |
2012 |
|
Spinal Muscular Atrophy
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
One of the responsible genes for SMA is the survival motor neuron (SMN) gene, which is homozygously absent or interrupted in more than 90% of SMA patients.
|
9153454 |
1997 |
|
Spinal Muscular Atrophy
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Our findings as well as those of other authors show that an increased number of SMN2 copies in healthy carriers of the biallelic SMN1 deletion is an important SMA phenotype modifier, but probably not the only one.
|
18337729 |
2008 |
|
Spinal Muscular Atrophy
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
Primary hits were further evaluated for their ability to correct the splicing defect and resultant increase of SMN activity in SMA patient-derived fibroblasts.
|
31563042 |
2019 |
|
Spinal Muscular Atrophy
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
This R1810me2s modification requires protein arginine methyltransferase 5 (PRMT5) and recruits the Tudor domain of the survival of motor neuron (SMN, also known as GEMIN1) protein, which is mutated in spinal muscular atrophy.
|
26700805 |
2016 |
|
Spinal Muscular Atrophy
|
0.700 |
Biomarker
|
disease |
BEFREE |
Our results confirm the variability in the number of NAIP signals in non-SMA chromosomes (2-6) and show that SMN is present on average twice per chromosome although in one chromosome 4-5 signals for the SMN-containing cosmid probe were detected.
|
9067434 |
1996 |
|
Spinal Muscular Atrophy
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Spinal muscular atrophy: a new player joins the battle for SMN2 exon 7 splicing.
|
20890126 |
2010 |
|
Spinal Muscular Atrophy
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
An asymptomatic individual with homozygous deletion of exons 7 and 8 of the SMN gene showed no difference in microsatellite markers in the SMA-related 5q11.2-5q13.3.
|
9341874 |
1997 |
|
Spinal Muscular Atrophy
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Spinal Muscular Atrophy type 1 (SMA1) is a rare genetic neuromuscular disease where 75% of SMA1 patients die/require permanent-ventilation by 13.6 months.
|
30548438 |
2019 |
|
Spinal Muscular Atrophy
|
0.700 |
Biomarker
|
disease |
BEFREE |
We therefore investigated the expression of circadian rhythm genes in various metabolic tissues and spinal cord of the Taiwanese Smn-/-;SMN2 SMA animal model.
|
29982483 |
2018 |