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Genetic Modifiers of the Spinal Muscular Atrophy Phenotype

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Abstract

Proximal spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease caused by homozygous deletion in the seventh exon of the SMN1 gene. The aim of this work is to analyze the association of the allelic polymorphism of telomeric genes SMN1 and NAIP and the centromeric gene SMN2 of the 5q13 region with the clinical phenotype of SMA. It was shown that the homozygous genotype, which contains a telomeric deletion, covering both SMN1 and NAIP, is significantly more often observed in patients with the most severe type of SMA. Three or more copies of SMN2 are associated with a milder phenotype; the number of SMN2 copies affects the SMA phenotype more heavily than the length of the telomeric deletion. It was shown that one SMN2 copy is significantly more frequent than three or more copies of this gene in SMA-patients with homozygous deletion of SMN1 and NAIP. This fact may indicate the presence of a large deletion of all the three studied genes in SMA genotypes associated with the most severe type of SMA. It is noted that congenital SMA (type 0) is significantly less common in female patients, which may indicate the presence of SMA modifier genes on the X-chromosome.

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ACKNOWLEDGMENTS

We thank the Kharkiv Charity Foundation Children with Spinal Muscular Atrophy headed by V.N. Matyushenko for many years of comprehensive assistance in the research of this disease and the popularization of knowledge about SMA among the population of Ukraine. We also thank the doctors of the medical-genetic centers of Ukraine for collecting and analyzing clinical data of patients. We thank the staff of the Human Genomics Department of the IMBG NAS of Ukraine, primarily A.Yu. Ekshiyan, A.B. Livshits, A.A. Solov’ev, and S.S. Podlesnaya, who actively participated in the formation of the collection of DNA samples from patients with SMA and in the genotyping of patients by SMN1 and NAIP in the period of 1995—2016.

Funding

This work was carried out in the framework of the budget topics of the IMGB NAS of Ukraine 2011–2015 (topic code 2.2.4.13, state registration number 0105U005341) and 2016–2020 (topic code 2.2.4.13, state registration number 0115U003747).

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Authors and Affiliations

  1. Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 03680, Kyiv, Ukraine

    N. V. Hryshchenko & L. A. Livshits

  2. Educational and Scientific Center Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, 03022, Kyiv, Ukraine

    A. A. Yurchenko & H. S. Karaman

Authors
  1. N. V. Hryshchenko
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  2. A. A. Yurchenko
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  3. H. S. Karaman
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  4. L. A. Livshits
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Correspondence to N. V. Hryshchenko.

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Statement of compliance with standards of research involving humans as subjects. All procedures carried out in the studies involving people were consistent with international and national standards, the Helsinki Declaration of 1964, and its later amendments, and approved by the Bioethics Commission of the IMBG NAS of Ukraine.

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Translated by K. Lazarev

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Hryshchenko, N.V., Yurchenko, A.A., Karaman, H.S. et al. Genetic Modifiers of the Spinal Muscular Atrophy Phenotype. Cytol. Genet. 54, 130–136 (2020). https://doi.org/10.3103/S0095452720020073

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