Newborn screening for spinal muscular atrophy: Anticipating an imminent need

Phan, Han; Taylor, Jennifer L.; Hannon, Harry; Howell, R. Rodney

doi:10.1053/j.semperi.2015.03.006

Cited by 62 publications

(55 citation statements)

References 129 publications

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“…Common features that result from the degeneration and loss of anterior horn cells include motor delays, low muscle tone, proximal muscle weakness, and, in some cases, finger tremor and tongue fasciculation. SMA has an estimated incidence of one in 6000 to 11,000 live births (Darras 2015) and is not routinely screened for in state-required newborn screening panels (Phan et al 2015). Prognosis varies depending on the type of SMA and the degree of respiratory function (Darras 2015;Wirth 2000).…”

Section: Sma Overviewmentioning

confidence: 99%

A Review on Spinal Muscular Atrophy: Awareness, Knowledge, and Attitudes

Moultrie

Kish-Doto²,

Peay

et al. 2016

Journal of Genetic Counseling

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Spinal Muscular Atrophy (SMA) is one of the most common genetic causes of infant death. There is presently no cure, but the therapeutic pipeline is promising. Given the prevalence of SMA coupled with the potential for new treatment options, universal carrier screening, and newborn screening, we conducted a literature review of the awareness, knowledge, and attitudes held by the public and non-geneticist clinicians about various aspects of SMA. We then identify recommendations for targeting additional research, training, and educational efforts to increase awareness. In the limited available literature, we found that the public is generally unfamiliar with SMA but has favorable views of carrier and newborn screening. Clinicians also had limited understanding of SMA. Further research into knowledge and attitudes of healthcare providers and the general public will help develop a better understanding of education gaps and inform outreach efforts. These educational efforts are needed to complement the momentum as treatments are being developed and tested. Furthermore, professional societies are proposing routine carrier screening and SMA may achieve newborn screening status, which will change the SMA landscape for genetics professionals and families. Thus, it is important to explore knowledge and attitudes about SMA to allow us to prepare for when SMA attains higher public and clinician recognition.

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Section: Sma Overviewmentioning

confidence: 99%

A Review on Spinal Muscular Atrophy: Awareness, Knowledge, and Attitudes

Moultrie

Kish-Doto²,

Peay

et al. 2016

Journal of Genetic Counseling

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“…SMA is characterized by synaptic defects in the motor circuitry, especially at the neuromuscular junction (NMJ), and a dying-back axonopathy. This is followed by a gradual loss of motor neurons in the spinal cord, and results in progressive muscle weakness and eventual death due to respiratory distress (Phan et al, 2015). SMA is caused by reduced survival of motor neuron (SMN) protein levels due to either a deletion or mutation in the SMN1 gene .…”

Section: Introductionmentioning

confidence: 99%

The Survival of Motor Neuron Protein Acts as a Molecular Chaperone for mRNP Assembly

et al. 2017

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Summary Spinal muscular atrophy (SMA) is a motor neuron disease caused by reduced levels of the survival of motor neuron (SMN) protein. SMN is part of a multiprotein complex that facilitates the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs). SMN has also been found to associate with mRNA binding proteins but the nature of this association was unknown. Here we have employed a combination of biochemical and advanced imaging methods to demonstrate that SMN promotes the molecular interaction between IMP1 protein and the 3′ UTR zipcode region of β-actin mRNA, leading to assembly of messenger ribonucleoprotein complexes (mRNPs) that associate with the cytoskeleton to facilitate trafficking. We have identified defects in mRNP assembly in cells and tissues from SMA disease models and patients that depend on the SMN Tudor domain and explain the observed deficiency in mRNA localization and local translation, providing insight into SMA pathogenesis as an RNP-assembly disorder.

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“…One of the hurdles to treatment of patients with SMA is being able to recognize and diagnose them early, prior to the loss of irreplaceable motor neuron units. For SMA type 1, denervation begins within the first 3 months of life and more than 90% of motor units are lost within the first 6 months of age [29]. If newborn screening (NBS) was employed, patients could be identified and treatment initiated presymptomatically in a greater majority of patients.…”

Section: Standard Of Carementioning

confidence: 99%

“…In order for NBS to be feasible for SMA, it must be cost-efficient, high throughout, and easy to implement in various NBS laboratories. Results should have rapid turnaround (typically this is within 5 days) [29]. After initial screening, a second-tier test would likely be needed to confirm or quantify SMN1 number (deletions/mutations) and then evaluate for SMN2 copy number.…”

Section: Standard Of Carementioning

confidence: 99%

Treatment Advances in Spinal Muscular Atrophy

Bharucha‐Goebel

Kaufmann

2017

Curr Neurol Neurosci Rep

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Purpose of Review Spinal Muscular Atrophy (SMA) is a genetic disorder of motor neurons in the anterior horns of the spinal cord and brainstem that results in muscle atrophy and weakness. SMA is an autosomal recessive disease linked to deletions of the SMN1 gene on chromosome 5q. Humans have a duplicate gene (SMN2) whose product can mitigate disease severity, leading to the variability in severity and age of onset of disease, and is therefore a target for drug development. Recent Findings Advances in preclinical and clinical trials have paved the way for novel therapeutic options for SMA patients, including many currently in clinical trials. In 2016, the first treatment for SMA has been approved in the US, an antisense-oligonucleotide that increases full-length protein product derived from SMN2. Summary The approval of a first treatment for SMA and the rapid advances in clinical trials provide the prospect for multiple approaches to disease modification. There are several other promising therapeutics in different stages of development, based on approaches such as neuroprotection, or gene therapy.

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Newborn screening for spinal muscular atrophy: Anticipating an imminent need

Cited by 62 publications

References 129 publications

A Review on Spinal Muscular Atrophy: Awareness, Knowledge, and Attitudes

A Review on Spinal Muscular Atrophy: Awareness, Knowledge, and Attitudes

The Survival of Motor Neuron Protein Acts as a Molecular Chaperone for mRNP Assembly

Treatment Advances in Spinal Muscular Atrophy

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