scholarly journals SMN2 Gene

2020 ◽  
Author(s):  
Keyword(s):  
Smn2 Gene

scholarly journals Beyond copy number: A new, rapid and versatile method for sequencing the entire SMN2 gene in SMA patients

2021 ◽  
Author(s):  
Laura Blasco‐Pérez ◽  
Ida Paramonov ◽  
Jordi Leno ◽  
Sara Bernal ◽  
Laura Alias ◽  
...  
Keyword(s):  
Copy Number ◽  
Smn2 Gene

scholarly journals The RNA Binding Protein hnRNP Q Modulates the Utilization of Exon 7 in the Survival Motor Neuron 2 (SMN2) Gene

2008 ◽  
Vol 28 (22) ◽  
pp. 6929-6938 ◽  
Author(s):  
Hung-Hsi Chen ◽  
Jan-Growth Chang ◽  
Ruei-Min Lu ◽  
Tsui-Yi Peng ◽  
Woan-Yuh Tarn
Keyword(s):  
Rna Binding ◽  
Muscular Atrophy ◽  
Rna Binding Protein ◽  
Neuromuscular Disorder ◽  
Mrna Splicing ◽  
Survival Motor Neuron ◽  
Smn2 Gene ◽  
Smn Protein ◽  
High Level ◽  
Precursor Mrna

ABSTRACT Spinal muscular atrophy (SMA) is a recessive neuromuscular disorder caused by the homozygous loss of the SMN1 gene. The human SMN2 gene has a C-to-T transition at position +6 of exon 7 and thus produces exon 7-skipping mRNAs. However, we observed an unexpectedly high level of exon 7-containing SMN2 transcripts as well as SMN protein in testis of smn −/− SMN2 transgenic mice. Using affinity chromatography, we identified several SMN RNA-associating proteins in mouse testis and human HeLa cells, including hnRNP Q. The major hnRNP Q isoform, Q1, directly bound SMN exon 7 in the vicinity of nucleotide +6. Overexpression of hnRNP Q1 promoted the inclusion of exon 7 in SMN2, probably by activating the use of its upstream 3′ splice site. However, the minor isoforms Q2/Q3 could antagonize the activity of hnRNP Q1 and induced exon 7 exclusion. Intriguingly, enhanced exon 7 inclusion was also observed upon concomitant depletion of three hnRNP Q isoforms. Thus, differential expression of hnRNP Q isoforms may result in intricate control of SMN precursor mRNA splicing. Here, we demonstrate that hnRNP Q is a splicing modulator of SMN, further underscoring the potential of hnRNP Q as a therapeutic target for SMA.

P.6.5 Improved antisense oligonucleotide design to suppress aberrant SMN2 gene transcript processing

2013 ◽  
Vol 23 (9-10) ◽  
pp. 771
Author(s):  
C. Mitrpant ◽  
P.N. Porensky ◽  
H. Zhou ◽  
L. Price ◽  
F. Muntoni ◽  
...  
Keyword(s):  
Antisense Oligonucleotide ◽  
Gene Transcript ◽  
Transcript Processing ◽  
Smn2 Gene

Spinal Muscular Atrophy

2017 ◽  
Author(s):  
Arthur H. M. Burghes ◽  
Vicki L. McGovern
Keyword(s):  
Motor Neuron ◽  
Gene Locus ◽  
Autosomal Recessive ◽  
Muscular Atrophy ◽  
Autosomal Recessive Disorder ◽  
Clinical Testing ◽  
Smn1 Gene ◽  
Smn2 Gene ◽  
Spinal Muscular Atrophies ◽  
Smn Gene

Spinal muscular atrophies affect the lower motor neuron. The most common SMA maps to 5q is an autosomal recessive disorder. SMA is caused by loss or mutation of the SMN1 gene and retention of the SMN2 gene, and these genes lie in a complex area of the genome. Mild missense alleles of SMN1 work to complement SMN2 to give function and therapeutics that restore SMN levels are in clinical testing. Modifiers that lie outside the SMN gene locus and influence severity clearly exist, but what they are remains unknown as do the critical genes affected by SMN deficiency.

scholarly journals Identification of Novel Compounds That Increase SMN Protein Levels Using an Improved SMN2 Reporter Cell Assay

2012 ◽  
Vol 17 (4) ◽  
pp. 481-495 ◽  
Author(s):  
Jonathan J. Cherry ◽  
Matthew C. Evans ◽  
Jake Ni ◽  
Gregory D. Cuny ◽  
Marcie A. Glicksman ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Neurodegenerative Disorder ◽  
Muscular Atrophy ◽  
Full Length ◽  
Reporter Cell ◽  
Protein Levels ◽  
Smn2 Gene ◽  
Smn Protein ◽  
Neuron Function ◽  
Survival Of Motor Neuron

Spinal muscular atrophy (SMA) is a neurodegenerative disorder that is characterized by progressive loss of motor neuron function. It is caused by the homozygous loss of the SMN1 ( survival of motor neuron 1) gene and a decrease in full-length SMN protein. SMN2 is a nearly identical homolog of SMN1 that, due to alternative splicing, expresses predominantly truncated SMN protein. SMN2 represents an enticing therapeutic target. Increasing expression of full-length SMN from the SMN2 gene might represent a treatment for SMA. We describe a newly designed cell-based reporter assay that faithfully and reproducibly measures full-length SMN expression from the SMN2 gene. This reporter can detect increases of SMN protein by an array of compounds previously shown to regulate SMN2 expression and by the overexpression of proteins that modulate SMN2 splicing. It also can be used to evaluate changes at both the transcriptional and splicing level. This assay can be a valuable tool for the identification of novel compounds that increase SMN2 protein levels and the optimization of compounds already known to modulate SMN2 expression. We present here preliminary data from a high-throughput screen using this assay to identify novel compounds that increase expression of SMN2.

scholarly journals The c.859G>C variant in the SMN2 gene is associated with types II and III SMA and originates from a common ancestor

2010 ◽  
Vol 47 (9) ◽  
pp. 640-642 ◽  
Author(s):  
S. Bernal ◽  
L. Alias ◽  
M. J. Barcelo ◽  
E. Also-Rallo ◽  
R. Martinez-Hernandez ◽  
...  
Keyword(s):  
Common Ancestor ◽  
Smn2 Gene

scholarly journals Mutation analysis of 419 family and prenatal diagnosis of 339 cases of spinal muscular atrophy in China

2020 ◽  
Author(s):  
Yingjie Sun ◽  
Xiangdong Kong ◽  
Zhenhua Zhao ◽  
Xuechao Zhao
Keyword(s):  
Prenatal Diagnosis ◽  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Point Mutations ◽  
Homozygous Deletion ◽  
Common Mutation ◽  
Type I ◽  
Copy Numbers ◽  
Smn2 Gene ◽  
The Impact

Abstract Background Spinal muscular atrophy (SMA) is a common and lethal autosomal recessive neurodegenerative disease caused by mutations in the survival motor neuron 1 (SMN1) gene. At present, gene therapy medicine for SMA, i.e., Spinraza (Nusinersen), has been approved by the FDA, bringing hope to SMA patients and families. Accurate diagnosis is essential for treatment. Our goal was to detect genetic mutations in SMA patients in China and to show the results of the prenatal diagnosis of SMA.Methods In this study, we examined 419 patients in our hospital from January 2010 to September 2019. Multiplex ligation-dependent probe amplification analysis was used to determine the copy numbers of SMN1 and SMN2. Long-range PCR combined with nested PCR was used to detect point mutations in SMN1. In addition to the above detection methods, we also used QF-PCR in prenatal diagnosis to reduce the impact of maternal contamination. We conducted a total of 339 prenatal diagnoses from January 2010 to September 2019.Results Homozygous deletion of SMN1 exon 7 was detected in 96.40% (404/419) of patients. Homozygous deletion of SMN1 exon 7 alone was detected in 15 patients (3.60%). In total, 10 point mutations were detected in the 15 pedigrees. Most patients with SMA Type I have 1~2 copies of the SMN2 gene. Patients with SMA Type II have 2 or 3 copies of the SMN2 gene. The results of prenatal diagnoses showed that 118 fetuses were normal, 149 fetuses were carriers of heterozygous variants, and the remaining 72 fetuses harbored compound heterozygous variants or homozygous variants. Conclusions Our study found that the most common mutation in SMA was homozygous deletion of SMN1 exon 7 in our study. We suggest that detecting only the deletion of exon 7 of SMN1 can meet most of the screening needs. We also believe that SMN2 copy numbers can help infer the disease classification and provide some reference for future treatment options.

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