Spinal Muscular Atrophy Results and Comparison of Commonly Used Methods
Abstract
Aim: We aimed to share our genetic test results for SMA since 2001, and compare the commonly used screening and diagnostic methods for SMA.
Materials and Methods: The subjects consist of 222 individuals including SMA cases and their relatives, who referred our center for the investigation of SMA between the years 2001-2019. The results of Restriction Fragment Length Polymorphism (RFLP) between 2001-2015 years and Multiplex Ligation-dependent Probe Amplification (MLPA) between 2015-2019 years are investigated. RFLP is also used for selected cases after 2015.
Results: There is no prominent difference in diagnosis of SMA cases between methods. About 18% of the samples have homozygous SMN1 exon 7-8 deletion. MLPA is better in determining the variants owing to SMN2 gene.
Conclusion: There is no evident difference between the methods in the diagnosis of SMA. But, because of its ability in screening heterozygous SMA carriers and superiority in determining the SMN2 copy number, the MLPA is markedly more successful. RFLP is kept as second method for special cases and used when confirmation is needed. In addition to these widely used techniques, there is a need for commonly used tests that able to detect SMN1 point mutations (2-5% of SMA cases) and identify if 2 SMN1 copies which are present on the same chromosome; the situation has a frequency of 3.6% in population.
References
Rashnonejad A, Onay H, Atik T, Atan Sahin O, Gokben S, Tekgul H, et al. Molecular Genetic Analysis of Survival Motor Neuron Gene in 460 Turkish Cases with Suspicious Spinal Muscular Atrophy Disease. Iran J child Neurol [Internet]. 2016;10(4):30–5.
Prior TW, Finanger E. Spinal Muscular Atrophy [Internet]. GeneReviews®. University of Washington, Seattle; 1993.
Singh RN, Singh NN. Mechanism of splicing regulation of spinal muscular atrophy genes. In: Advances in Neurobiology [Internet]. 2018. p. 31–61.
Kariyawasam D, Carey KA, Jones KJ, Farrar MA. New and developing therapies in spinal muscular atrophy. Paediatr Respir Rev [Internet]. 2018 Sep;28:3–10.
Butchbach MER. Copy Number Variations in the Survival Motor Neuron Genes: Implications for Spinal Muscular Atrophy and Other Neurodegenerative Diseases. Front Mol Biosci [Internet]. 2016 Mar 10;3:7.
Kerr DA, Nery JP, Traystman RJ, Chau BN, Hardwick JM. Survival motor neuron protein modulates neuron-specific apoptosis. Proc Natl Acad Sci U S A [Internet]. 2000 Nov 21;97(24):13312–7.
Farrar MA, Kiernan MC. The Genetics of Spinal Muscular Atrophy: Progress and Challenges. Neurotherapeutics [Internet]. 2015 Apr 21;12(2):290–302.
Chaytow H, Huang YT, Gillingwater TH, Faller KME. The role of survival motor neuron protein (SMN) in protein homeostasis. Cell Mol Life Sci [Internet]. 2018 Nov 5;75(21):3877–94.
Darras BT. Non-5q spinal muscular atrophies: the alphanumeric soup thickens. Neurology [Internet]. 2011 Jul 26;77(4):312–4.
Peeters K, Chamova T, Jordanova A. Clinical and genetic diversity of SMN1-negative proximal spinal muscular atrophies. Brain [Internet]. 2014 Nov;137(11):2879–96.
Goodkey K, Aslesh T, Maruyama R, Yokota T. Nusinersen in the Treatment of Spinal Muscular Atrophy. Methods Mol Biol [Internet]. 2018 Oct 3;1828(10):69–76.
Chiriboga CA. Nusinersen for the treatment of spinal muscular atrophy. Expert Rev Neurother [Internet]. 2017 Oct 3;17(10):955–62.
Talbot K, Tizzano EF. The clinical landscape for SMA in a new therapeutic era. Gene Ther [Internet]. 2017 Sep 20;24(9):529–33.
MacDonald WK, Hamilton D, Kuhle S. SMA carrier testing: a meta-analysis of differences in test performance by ethnic group. Prenat Diagn [Internet]. 2014 Dec;34(12):1219–26.
Phan HC, Taylor JL, Hannon H, Howell R. Newborn screening for spinal muscular atrophy: Anticipating an imminent need. Semin Perinatol [Internet]. 2015 Apr;39(3):217–29.
Wirth B. An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA). Hum Mutat [Internet]. 2000 Mar;15(3):228–37.
