2023 / 03

DOI: 10.24075/brsmu.2023.025

ORIGINAL RESEARCH

Detection of SMN1 loss with PCR-based screening test

Nazarov VD1, Cherebillo CC1, Lapin SV1, Sidorenko DV1, Devyatkina YA1, Musonova AC1, Petrova TV2, Nikiforova AI2, Ivanova AV2
About authors

1 Federal State Budgetary Educational Institution of Higher Education Academician I.P. Pavlov First St. Petersburg State Medical University of the Ministry of Healthcare of Russian Federation, Russia

2 DNA-Technology LLC, Moscow, Russia

Correspondence should be addressed: Carina C. Cherebillo
6/8, Lva Tolstogo, Saint-Petersburg, 197022, Russia: ur.liam@olliberehc.k

About paper

Funding: All tests was provided by DNA-Technology LLC.

Author contribution: Nazarov VD, Lapin SV — concept; Sidorenko DV, Devyatkina YA, Musonova AC — investigation; Petrova TV, Nikiforova AI, Ivanova AV — methodology; Nazarov VD, Cherebillo CC — wrining, original draft preparation; Cherebillo CC, Lapin SV, Petrova TV, Nikiforova AI, Ivanova AV — writing, review & editing.

Compliance with ethical standards: this study was approved by the local Ethics Committee of the Pavlov First Saint Petersburg State Medical University (№ 274 from 26.06.2023). Written informed consent was obtained from all participants or their parents. The 1975 Declaration of Helsinki was rigorously adhered to secure the rights of the patients.

Received: 2023-05-30 Accepted: 2023-06-22 Published online: 2023-06-30
|
  1. Butchbach MER. Genomic variability in the survival motor neuron genes (SMN1 and SMN2): Implications for spinal muscular atrophy phenotype and therapeutics development. Int J Mol Sci. 2021; 22 (15): 7896. DOI: 10.3390/ijms22157896.
  2. Chien YH, Chiang SC, Weng WC, Lee NC, Lin CJ, Hsieh WS, et al. Presymptomatic Diagnosis of Spinal Muscular Atrophy Through Newborn Screening. J Pediatr. 2017; 190: 124–129. DOI: 10.1016/j.jpeds.2017.06.042.
  3. Nicolau S, Waldrop MA, Connolly AM, Mendell JR. Spinal Muscular Atrophy. Semin Pediatr Neurol. 2021; 37: 100878. DOI: 10.1016/j.spen.2021.100878.
  4. Clermont O, Burlet P, Benit P, Chanterau D, Saugier-Veber P, Munnich A, et al. Molecular analysis of SMA patients without homozygous SMN1 deletions using a new strategy for identification of SMN1 subtle mutations. Hum Mutat. 2004; 24 (5): 417–27. DOI: 10.1002/humu.20092.
  5. Zabnenkova VV, Dadali EL, Spiridonova MG, Zinchenko RA, Polyakov AV. Spinal muscular atrophy carrier frequency in Russian Federation. ASHG. 2016. DOI: 10.13140/RG.2.2.16245.60642.
  6. Arnold ES, Fischbeck KH. Spinal muscular atrophy. Handb Clin Neurol. 2018; 148: 591–601. DOI: 10.1016/B978-0-444-640765.00038-7.
  7. Ministerstvo zdravooxraneniya Rossijskoj Federacii. Klinicheskie rekomendacii «Proksimal'naya spinal'naya myshechnaya atrofiya 5q». M., 2023. Russian.
  8. Gambardella A, Mazzei R, Toscano A, Annesi G, Pasqua A, Annesi F, et al. Spinal muscular atrophy due to an isolated deletion of exon 8 of the telomeric survival motor neuron gene. Ann Neurol. 1998; 44 (5): 836–39. DOI: 10.1002/ana.410440522.
  9. Stabley DL, Holbrook J, Scavina M, Crawford TO, Swoboda KJ, Robbins KM, et al. Detection of SMN1 to SMN2 gene conversion events and partial SMN1 gene deletions using array digital PCR. Neurogenetics. 2021; 22 (1): 53–64. DOI: 10.1007/s10048-02000630-5.
  10. Niba ETE, Nishio H, Wijaya YOS, Lai PS, Tozawa T, Chiyonobu T, et al. Clinical phenotypes of spinal muscular atrophy patients with hybrid SMN gene. Brain Dev. 2021; 43 (2): 294–302. DOI: 10.1016/j.braindev.2020.09.005.
  11. Lutz CM, Kariy S, Patruni S, Osborne MA, Liu D, Henderson CE, et al. Postsymptomatic restoration of SMN rescues the disease phenotype in a mouse model of severe spinal muscular atrophy. J Clin Invest. 2011; 121 (8): 3029–41. DOI: 10.1172/JCI57291.
  12. Comley LH, Kline RA, Thomson AK, Woschitz V, Landeros EV, Osman EY, et al. Motor unit recovery following Smn restoration in mouse models of spinal muscular atrophy. Hum Mol Genet. 2022; 31 (18): 3107–19. DOI: 10.1093/hmg/ddac097.
  13. De Vivo DC, Bertini E, Swoboda KJ, Hwu WL, Crawford TO, Finkel RS, et al. Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study. Neuromuscul Disord. 2019; 29 (11): 842–56. DOI: 10.1016/j.nmd.2019.09.007.
  14. Strauss КА, Farrar МА, Muntoni F, Saito К, Mendell JR, Servais L, et al. Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial. Nat Med. 2022; 28 (7): 1390–7. DOI: 10.1038/s41591-022-01867-3.
  15. Order of the Ministry of Health of the Russian Federation № 274n dated 21.04.2022 "On approval of the Procedure for providing medical care to patients with congenital and (or) hereditary diseases".
  16. Stuppia L, Antonucci I, Palka G, Gatta V. Use of the MLPA Assay in the Molecular Diagnosis of Gene Copy Number Alterations in Human Genetic Diseases. Int J Mol Sci. 2012; 13: 3245–76. DOI: 10.3390/ijms13033245.
  17. Arkblad EL, Darin N, Berg K, Kimber E, Brandberg G, Lindberg C, et al. Multiplex ligation-dependent probe amplification improves diagnostics in spinal muscular atrophy. Neuromuscul Disord. 2006; 16: 830–38.
  18. Feldkötter M, Schwarzer V, Wirth R, Wienker TF, Wirth B. Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am J Hum Genet. 2002; 70 (2): 358–68. DOI: 10.1086/338627.
  19. Gómez-Curet I, Robinson KG, Funanage VL, Crawford TO, Scavina M, Wang W. Robust quantification of the SMN gene copy number by real-time TaqMan PCR. Neurogenetics. 2007; 8 (4): 271–8. DOI: 10.1007/s10048-007-0093-1.
  20. Gutierrez-Mateo C, Timonen A, Vaahtera K, Jaakkola M, Hougaard DM, Bybjerg-Grauholm J. Development of a Multiplex Real-Time PCR Assay for the Newborn Screening of SCID, SMA, and XLA. Int J Neonatal Screen. 2019; 5 (4): 39. DOI: 10.3390/ijns5040039.
  21. Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995; 80 (1): 155–65. DOI: 10.1016/0092-8674(95)90460-3.
  22. Kraszewski JN, Kay DM, Stevens CF, Koval C, Haser B, Ortiz V, et al. Pilot study of population-based newborn screening for spinal muscular atrophy in New York state. Genet Med. 2018; 20 (6): 608–13. DOI: 10.1038/gim.2017.152.
  23. Kariyawasam DST, Russell JS, Wiley V, Alexander IE, Farrar MA. The implementation of newborn screening for spinal muscular atrophy: the Australian experience. Genet Med. 2020; 22 (3): 557–65. DOI: 10.1038/s41436-019-0673-0.