Genetic modifiers of spinal muscular atrophy phenotype

Hryshchenko N.V., Karaman H.S., Yurchenko A.A., Livshits L.A.

SUMMARY. Proximal spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease caused by a homozygous deletion in SMN1 gene exon 7. The aim of the work is to analyze an association of the allelic polymorphism of the telomeric genes SMN1, NAIP and the centromeric gene SMN2 of 5q13 region with the clinical phenotype of SMA. It has been 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 has been shown that in SMA-patients with a homozygous deletion of SMN1 and NAIP one copy of SMN2 is significantly more frequent than three or more copies of this gene. This fact may indicate a presence of a large deletion of all 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 X-chromosome.

Key words: spinal muscular atrophy, SMN1, NAIP, SMN2, phenotype, gender

Tsitologiya i Genetika 2020, vol. 54, no. 2, pp. 52-60

1. Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine,
   03680, Kiev, ul. akademika Zabolotnogo, 150, Ukraine
2. Еducational and Scientific Centre «Institute of Biology and Medicine» of Taras Shevchenko National University of Kiev, 03022, Kiev, avenue academician Glushkov 2, Ukraine

E-mail: dnatest imbg.org.ua

Hryshchenko N.V., Karaman H.S., Yurchenko A.A., Livshits L.A. Genetic modifiers of spinal muscular atrophy phenotype, Tsitol Genet., 2020, vol. 54, no. 2, pp. 52-60.

In "Cytology and Genetics":
N. V. Hryshchenko, A. A. Yurchenko, H. S. Karaman & L. A. Livshits Genetic Modifiers of the Spinal Muscular Atrophy Phenotype, Cytol Genet., 2020, vol. 54, no. 2, pp. 130–136
DOI: 10.3103/S0095452720020073

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