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Clinical and biochemical polymorphism of spinal muscular atrophy

https://doi.org/10.14412/2074-2711-2017-1-50-54

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Abstract

Objective: to conduct clinical laboratory studies of spinal muscular atrophy (SMA) for the clarification of the pathogenetic features and role of neurotrophic factors in the formation of polymorphism of this disease

Patients and methods. Thirty-five patients aged 9 months to 53 years (mean age, 14.5 years) with different inherited forms of SMA were examined. Clinical, genealogical, and laboratory tests were carried out. A control group consisted of 40 healthy individuals aged 7–45 years (mean age, 16.5 years). The levels of neurotrophins, such as brain-derived growth factor (BDGF), nerve growth factor (NGF), and ciliary neurotrophic factor (CNTF) in serum samples were determined by enzyme immunoassay.

Results. Changes in the expression of the neurotrophic factors were found in patients with SMA. The enzyme immunoassay data suggest that the serum concentrations of BDGF, NGF, and CNTF in patients with SMA were significantly higher than those in healthy controls. The group of SMA patients aged under 18 years showed a statistically significant (p<0.001) increase in NGF concentrations (3680±936 ng/ml) versus the control group of the same age (625±444 pg/ml).

Conclusion. In our opinion, the clinical polymorphism of SMA can be explained by the polymorphism of various pathogenic factors: genetic, morphofunctional, and biochemical ones. Overexpression of neurotrophins was first noticed to play a role in the development of more severe clinical types of SMA (proximal SMA), which may be related to both the ontogenetic features of children's age and disease duration. The study results can be further used to choose pathogenetic personalized therapy for SMA.

About the Authors

M. G. Sokolova
I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia
Russian Federation
41, Kirochnaya St., Saint Petersburg 119015


S. V. Lobzin
I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia
Russian Federation
41, Kirochnaya St., Saint Petersburg 119015


I. V. Litvinenko
S.M. Kirov Military Medical Academy, Ministry of Defense of Russia
Russian Federation
2, Lesnoy Prospect, Vyborg District, Saint Petersburg 194044


M. V. Rezvantsev
S.M. Kirov Military Medical Academy, Ministry of Defense of Russia
Russian Federation
2, Lesnoy Prospect, Vyborg District, Saint Petersburg 194044


L. A. Polyakova
I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia
Russian Federation
41, Kirochnaya St., Saint Petersburg 119015


References

1. Гусев ЕИ, редактор. Неврология: национальное руководство. Москва: ГЭОТАР-Медиа; 2009. 936 с. [Gusev EI, editor. Neurology. National Guide. Under edition RAS academician Gusev E.I. Moscow: GEOTARMedia; 2009. 936 p.]

2. Sumner CJ. Molecular mechanisms of spinal muscular atrophy. J Child Neurol. 2007 Aug;22(8): 979-89.

3. Blais M, Lеvesque P, Bellenfant S, Berthod F. Nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 and glial-derived neurotrophic factor enhance angiogenesis in a tissueengineered in vitro model. Tissue Eng Part A. 2013 Aug;19(15- 16):1655-64. doi: 10.1089/ten.tea.2012.0745. Epub 2013 Mar 26.

4. Huang EJ, Reichardt LF. Neurotrophins. Roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677-736.

5. He YY, Zhang XY, Yung WH, et al. Role of BDNF in central motor structures and motor diseases. Mol Neurobiol. 2013 Dec;48(3):783-93. doi: 10.1007/s12035-013-8466-y. Epub 2013 May 7.

6. Levi-Montalchini R. The nerve growth factor. 35 years later. Science. 1987 Sep 4;237(4819): 1154-62.

7. Sun XL, Chen BY, Duan L, et al. The proform of glia cell line-derived neurotrophic factor: a potentially biologically active protein. Mol Neurobiol. 2014 Feb;49(1):234-50. doi: 10.1007/s12035-013-8515-6. Epub 2013 Aug 10.

8. Ogino S, Wilson RB. Spinal muscular atrophy: molecular genetics and diagnostics. Expert Rev Mol Diagn. 2004 Jan;4(1):15-29.

9. Wirth B, Brichta L, Schrank B, et al. Mildly affected patients with spinal muscular atrophy are partially protected by an increased SMN2 copy number. Hum Genet. 2006 May;119(4): 422-8. Epub 2006 Mar 1.

10. Prior TW, Swoboda KJ, Scott HD, et al. Homozygous SMN1 deletions in unaffected family members and modification of the phenotype by SMN2. Am J Med Genet A. 2004 Oct 15; 130A(3):307-10.

11. Забненкова ВВ, Дадали ЕЛ, Поляков АВ. Модифицирующие факторы, оказывающие влияние на тяжесть течения спинальных мышечных атрофий I— IV типов. Медицинская генетика. 2011;(5):15-21. [Zabnenkova VV, Dadali EL, Polyakov AV. The modifying factors influenced on the severity of spinal muscular atrophy, type I—III. Meditsinskaya genetika. 2011;(5):15-21. (In Russ.)].

12. Arkblad Е, Tulinius М, Kroksmark АК, et al. A population-based study of genotypic and phenotypic variability in children with spinal muscular atrophy. Acta Paediatr. 2009 May;98(5): 865-72. doi: 10.1111/j.1651-2227.2008.01201.x. Epub 2009 Jan 20.

13. Oprea GE, Krober S, McWhorter ML, et al. Plastin 3 Is a Protective Modifier of Autosomal Recessive Spinal Muscular Atrophy. Science. 2008 Apr 25;320(5875):524-7. doi: 10.1126/science.1155085.

14. Jedrzejowska М, Milewski М, Zimowski J, et al. Phenotype modifiers of spinal muscular atrophy: the number of SMN2 gene copies, deletion in the NAIP gene and probably gender influence the course of the disease. Acta Biochim Pol. 2009;56(1):103-8. Epub 2009 Mar 14.

15. Le TT, Pham LT, Butchbach ME, et al. SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN. Hum Mol Genet. 2005 Mar 15;14(6):845-57. Epub 2005 Feb 9.

16. Соколова МГ, Пеннияйнен ВА, Резванцев МВ и др. Оценка реиннервационного процесса у больных спинальной мышечной атрофией 2 типа в комплексном клинико- экспериментальном исследовании. Вестник СЗГМУ. 2014;6(4):45-52. [Sokolova MG, Penniyainen VA, Rezvantsev MV, et al. Study of reinnervation process in patients with 2 type of spinal muscular atrophy: clinical experimental study. Vestnik SZGMU. 2014;6(4):45- 52. (In Russ.)].


For citation:


Sokolova M.G., Lobzin S.V., Litvinenko I.V., Rezvantsev M.V., Polyakova L.A. Clinical and biochemical polymorphism of spinal muscular atrophy. Neurology, Neuropsychiatry, Psychosomatics. 2017;9(1):50-54. (In Russ.) https://doi.org/10.14412/2074-2711-2017-1-50-54

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ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)