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PGT-M for spinocerebellar ataxia type 1: development of a STR panel and a report of two clinical cases

  • Genetics
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Abstract

Purpose

To present the developed preimplantation genetic testing (PGT) for spinocerebellar ataxia type 1 (SCA1) and the outcomes of IVF with PGT.

Methods

PGT was performed for two unrelated couples from the Republic of Sakha (Yakutia) with the risk of SCA1 in one spouse. We have developed a system for PGT of a monogenic disease (PGT-M) for SCA1, which includes the analysis of a panel of 11 polymorphic STR markers linked to the ATXN1 gene and a pathogenic variant of the ATXN1 gene using nested PCR and fragment analysis. IVF/ICSI programs were performed according to standard protocols. Multiple displacement amplification (MDA) was used for whole genome amplification (WGA) and array comparative genomic hybridization (aCGH) for aneuploidy testing (PGT-A).

Results

Eight STRs were informative for the first couple and ten for the second. Similarity of the haplotypes carrying pathogenic variants of the ATXN1 gene was noted. In the first case, during IVF/ICSI-PGT, three embryos reached the blastocyst stage and were biopsied. One embryo was diagnosed as normal by maternal STR haplotype and the ATXN1 allele. PGT-A revealed euploidy. The embryo transfer resulted in a singleton pregnancy, and a healthy boy was born. Postnatal diagnosis confirmed normal ATXN1. In the second case, two blastocysts were biopsied. Both were diagnosed as normal by PGT-M, but PGT-A revealed aneuploidy.

Conclusion

Birth of a healthy child after PGT for SCA1 was the first case of successful preimplantation prevention of SCA1 for the Yakut couple and the first case of successful PGT for SCA1 in Russia.

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Funding

This work was supported by the Ministry of Science and Higher Education of the Russian Federation (the Federal scientific-technical program for genetic technologies development for 2019–2027, agreement. 075–15-2021–1061, RF 193021X0029).

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Authors and Affiliations

  1. Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia

    Elena V. Soloveva, Maria M. Skleimova, Larisa I. Minaycheva, Anna F. Garaeva, Daria I. Zhigalina, Gulnara N. Seitova, Igor N. Lebedev & Vadim A. Stepanov

  2. ART Center of the Siberian State Medical University of the Ministry of Health of Russia, Tomsk, Russia

    Egor O. Churkin, Yulia V. Okkel, Oksana S. Timofeeva & Ilya A. Petrov

  3. Department of Obstetrics and Gynecology of the Siberian State Medical University of the Ministry of Health of Russia, Tomsk, Russia

    Oksana S. Timofeeva & Ilya A. Petrov

Authors
  1. Elena V. Soloveva
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  2. Maria M. Skleimova
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  9. Ilya A. Petrov
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Correspondence to Elena V. Soloveva.

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Soloveva, E.V., Skleimova, M.M., Minaycheva, L.I. et al. PGT-M for spinocerebellar ataxia type 1: development of a STR panel and a report of two clinical cases. J Assist Reprod Genet (2024). https://doi.org/10.1007/s10815-024-03105-w

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