Detection of Spinal Muscular Atrophy Patients Using Dried Saliva Spots

Spinal muscular atrophy (SMA) is a lower motor neuron disease, once considered incurable. The main symptoms are muscle weakness and muscular atrophy. More than 90% of cases of SMA are caused by homozygous deletion of survival motor neuron 1 (SMN1). Emerging treatments, such as splicing modulation of SMN2 and SMN gene replacement therapy, have improved the prognoses and motor functions of patients. However, confirmed diagnosis by SMN1 testing is often delayed, suggesting the presence of diagnosis-delayed or undiagnosed cases. To enable patients to access the right treatments, a screening system for SMA is essential. Even so, the current newborn screening system using dried blood spots is still invasive and cumbersome. Here, we developed a completely non-invasive screening system using dried saliva spots (DSS) as an alternative DNA source to detect SMN1 deletion. In this study, 60 DSS (40 SMA patients and 20 controls) were tested. The combination of modified competitive oligonucleotide priming-polymerase chain reaction and melting peak analysis clearly distinguished DSS samples with and without SMN1. In conclusion, these results suggest that our system with DSS is applicable to SMA patient detection in the real world.

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Spinal Muscular Atrophy Type B Awareness and Symptoms Prediction Using 3D Segmentation Process in MRI Images

International Journal of Scientific Research in Computer Science Engineering and Information Technology ◽

10.32628/cseit195142 ◽

2019 ◽

pp. 312-318

Author(s):

V. Manochithra ◽

G. Sumithra

Keyword(s):

Spinal Muscular Atrophy ◽

Motor Neuron ◽

Muscular Atrophy ◽

Homozygous Deletion ◽

Survival Motor Neuron ◽

Molecular Testing ◽

Prevention Measures ◽

Neuron Loss ◽

Motor Neuron Loss ◽

Smn Protein

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 deletion or mutation of the SMN1 gene allows efficient and specific diagnosis. In combination with loss of SMN1, patients retain variable numbers of copies of a second similar gene, SMN2, which produce reduced levels of the survival motor neuron (SMN) protein that are insufficient for normal motor neuron function. Despite the fact that the understanding of how ubiquitous reduction of SMN protein leads to motor neuron loss remains incomplete, several promising therapeutics are now being tested in early phase clinical trials. This proposed model investigates the symptoms and scans readings from the initial MRI scan images of babies with mutation progress and SMN proteins formation benchmark values for this particular disorder SMA and further this segmented parameters are acquitted into the K-means clustering technique that predict the report with the disorder symptoms with MSE (mean square error) values that helps the babies in future to take prevention measures to overcome this problem.

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New Treatments in Spinal Muscular Atrophy: Positive Results and New Challenges

Journal of Clinical Medicine ◽

10.3390/jcm9072222 ◽

2020 ◽

Vol 9 (7) ◽

pp. 2222 ◽

Cited By ~ 7

Author(s):

Sonia Messina ◽

Maria Sframeli

Keyword(s):

Spinal Muscular Atrophy ◽

Motor Neuron ◽

Muscular Atrophy ◽

Respiratory Muscles ◽

Gene Replacement ◽

Survival Motor Neuron ◽

Significant Disability ◽

New Challenges ◽

Smn Protein ◽

New Treatments

Spinal muscular atrophy (SMA) is one of the most common autosomal recessive diseases with progressive weakness of skeletal and respiratory muscles, leading to significant disability. The disorder is caused by mutations in the survival motor neuron 1 (SMN1) gene and a consequent decrease in the SMN protein leading to lower motor neuron degeneration. Recently, Food and Drug Administration (FDA) and European Medical Agency (EMA) approved the antisense oligonucleotide nusinersen, the first SMA disease-modifying treatment and gene replacement therapy by onasemnogene abeparvovec. Encouraging results from phase II and III clinical trials have raised hope that other therapeutic options will enter soon in clinical practice. However, the availability of effective approaches has raised up ethical, medical and financial issues that are routinely faced by the SMA community. This review covers the available data and the new challenges of SMA therapeutic strategies.

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Alternative Splicing Role in New Therapies of Spinal Muscular Atrophy

Genes ◽

10.3390/genes12091346 ◽

2021 ◽

Vol 12 (9) ◽

pp. 1346

Author(s):

Jan Lejman ◽

Grzegorz Zieliński ◽

Piotr Gawda ◽

Monika Lejman

Keyword(s):

Alternative Splicing ◽

Spinal Muscular Atrophy ◽

Motor Neuron ◽

Muscular Atrophy ◽

Neuromuscular Diseases ◽

Homozygous Deletion ◽

Survival Motor Neuron ◽

Biological Information ◽

Survival Motor Neuron Protein ◽

Attractive Therapeutic Target

It has been estimated that 80% of the pre-mRNA undergoes alternative splicing, which exponentially increases the flow of biological information in cellular processes and can be an attractive therapeutic target. It is a crucial mechanism to increase genetic diversity. Disturbed alternative splicing is observed in many disorders, including neuromuscular diseases and carcinomas. Spinal Muscular Atrophy (SMA) is an autosomal recessive neurodegenerative disease. Homozygous deletion in 5q13 (the region coding for the motor neuron survival gene (SMN1)) is responsible for 95% of SMA cases. The nearly identical SMN2 gene does not compensate for SMN loss caused by SMN1 gene mutation due to different splicing of exon 7. A pathologically low level of survival motor neuron protein (SMN) causes degeneration of the anterior horn cells in the spinal cord with associated destruction of α-motor cells and manifested by muscle weakness and loss. Understanding the regulation of the SMN2 pre-mRNA splicing process has allowed for innovative treatment and the introduction of new medicines for SMA. After describing the concept of splicing modulation, this review will cover the progress achieved in this field, by highlighting the breakthrough accomplished recently for the treatment of SMA using the mechanism of alternative splicing.

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