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Identification of novel variants in the LDLR gene in Russian patients with familial hypercholesterolemia using targeted sequencing

  • Authors:
    • Valentina V. Miroshnikova
    • Olga V. Romanova
    • Olga N. Ivanova
    • Mikhail A. Fedyakov
    • Alexandra A. Panteleeva
    • Yury A. Barbitoff
    • Maria V. Muzalevskaya
    • Sorejya A. Urazgildeeva
    • Victor S. Gurevich
    • Stanislav P. Urazov
    • Sergey G. Scherbak
    • Andrey M. Sarana
    • Natalia A. Semenova
    • Inga V. Anisimova
    • Darya M. Guseva
    • Sofya N. Pchelina
    • Andrey S. Glotov
    • Ekaterina Y. Zakharova
    • Oleg S. Glotov
  • View Affiliations / Copyright

    Affiliations: Laboratory of Human Molecular Genetics, Molecular and Radiation Biophysics Department, Petersburg Nuclear Physics Institute, National Research Center ‘Kurchatov Institute’, Gatchina 188300, Russian Federation, Genetic Laboratory of City Hospital No. 40, Saint‑Petersburg, 197706, Russian Federation, Laboratory of Hereditary Metabolic Diseases and Counselling Unit of Federal State Budgetary Institution ‘Research Centre for Medical Genetics’, Moscow 115522, Russian Federation, Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynaecology and Reproduction, Saint‑Petersburg 199034, Russian Federation, Department for Atherosclerosis and Lipid Disorders of North‑Western District Scientific and Clinical Center Named After L.G. Sokolov FMBA, Saint‑Petersburg 194291, Russian Federation, Medical Faculty of Saint‑Petersburg State University, Saint‑Petersburg 199034, Russian Federation
    Copyright: © Miroshnikova et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 15
    |
    Published online on: November 17, 2020
       https://doi.org/10.3892/br.2020.1391
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Abstract

Familial hypercholesterolemia (FH) is caused by mutations in various genes, including the LDLR, APOB and PSCK9 genes; however, the spectrum of these mutations in Russian individuals has not been fully investigated. In the present study, mutation screening was performed on the LDLR gene and other FH‑associated genes in patients with definite or possible FH, using next‑generation sequencing. In total, 59 unrelated patients were recruited and sorted into two separate groups depending on their age: Adult (n=31; median age, 49; age range, 23‑70) and children/adolescent (n=28; median age, 11; age range, 2‑21). FH‑associated variants were identified in 18 adults and 25 children, demonstrating mutation detection rates of 58 and 89% for the adult and children/adolescent groups, respectively. In the adult group, 13 patients had FH‑associated mutations in the LDLR gene, including two novel variants [NM_000527.4: c.433_434dupG p.(Val145Glyfs*35) and c.1186G>C p.(Gly396Arg)], 3 patients had APOB mutations and two had ABCG5/G8 mutations. In the children/adolescent group, 21 patients had FH‑causing mutations in the LDLR gene, including five novel variants [NM_000527.4: c.325T>G p.(Cys109Gly), c.401G>C p.(Cys134Ser), c.616A>C p.(Ser206Arg), c.1684_1691delTGGCCCAA p.(Pro563Hisfs*14) and c.940+1_c.940+4delGTGA], and 2 patients had APOB mutations, as well as ABCG8 and LIPA mutations, being found in different patients. The present study reported seven novel LDLR variants considered to be pathogenic or likely pathogenic. Among them, four missense variants were located in the coding regions, which corresponded to functional protein domains, and two frameshifts were identified that produced truncated proteins. These variants were observed only once in different patients, whereas a splicing variant in intron 6 (c.940+1_c.940+4delGTGA) was detected in four unrelated individuals. Previously reported variants in the LDLR, APOB, ABCG5/8 and LIPA genes were observed in 33 patients. The LDLR p.(Gly592Glu) variant was detected in 6 patients, representing 10% of the FH cases reported in the present study, thus it may be a major variant present in the Russian population. In conclusion, the present study identified seven novel variants of the LDLR gene and broadens the spectrum of mutations in FH‑related genes in the Russian Federation.
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Copy and paste a formatted citation
Spandidos Publications style
Miroshnikova VV, Romanova OV, Ivanova ON, Fedyakov MA, Panteleeva AA, Barbitoff YA, Muzalevskaya MV, Urazgildeeva SA, Gurevich VS, Urazov SP, Urazov SP, et al: Identification of novel variants in the <em>LDLR</em> gene in Russian patients with familial hypercholesterolemia using targeted sequencing. Biomed Rep 14: 15, 2021.
APA
Miroshnikova, V.V., Romanova, O.V., Ivanova, O.N., Fedyakov, M.A., Panteleeva, A.A., Barbitoff, Y.A. ... Glotov, O.S. (2021). Identification of novel variants in the <em>LDLR</em> gene in Russian patients with familial hypercholesterolemia using targeted sequencing. Biomedical Reports, 14, 15. https://doi.org/10.3892/br.2020.1391
MLA
Miroshnikova, V. V., Romanova, O. V., Ivanova, O. N., Fedyakov, M. A., Panteleeva, A. A., Barbitoff, Y. A., Muzalevskaya, M. V., Urazgildeeva, S. A., Gurevich, V. S., Urazov, S. P., Scherbak, S. G., Sarana, A. M., Semenova, N. A., Anisimova, I. V., Guseva, D. M., Pchelina, S. N., Glotov, A. S., Zakharova, E. Y., Glotov, O. S."Identification of novel variants in the <em>LDLR</em> gene in Russian patients with familial hypercholesterolemia using targeted sequencing". Biomedical Reports 14.1 (2021): 15.
Chicago
Miroshnikova, V. V., Romanova, O. V., Ivanova, O. N., Fedyakov, M. A., Panteleeva, A. A., Barbitoff, Y. A., Muzalevskaya, M. V., Urazgildeeva, S. A., Gurevich, V. S., Urazov, S. P., Scherbak, S. G., Sarana, A. M., Semenova, N. A., Anisimova, I. V., Guseva, D. M., Pchelina, S. N., Glotov, A. S., Zakharova, E. Y., Glotov, O. S."Identification of novel variants in the <em>LDLR</em> gene in Russian patients with familial hypercholesterolemia using targeted sequencing". Biomedical Reports 14, no. 1 (2021): 15. https://doi.org/10.3892/br.2020.1391
Copy and paste a formatted citation
x
Spandidos Publications style
Miroshnikova VV, Romanova OV, Ivanova ON, Fedyakov MA, Panteleeva AA, Barbitoff YA, Muzalevskaya MV, Urazgildeeva SA, Gurevich VS, Urazov SP, Urazov SP, et al: Identification of novel variants in the <em>LDLR</em> gene in Russian patients with familial hypercholesterolemia using targeted sequencing. Biomed Rep 14: 15, 2021.
APA
Miroshnikova, V.V., Romanova, O.V., Ivanova, O.N., Fedyakov, M.A., Panteleeva, A.A., Barbitoff, Y.A. ... Glotov, O.S. (2021). Identification of novel variants in the <em>LDLR</em> gene in Russian patients with familial hypercholesterolemia using targeted sequencing. Biomedical Reports, 14, 15. https://doi.org/10.3892/br.2020.1391
MLA
Miroshnikova, V. V., Romanova, O. V., Ivanova, O. N., Fedyakov, M. A., Panteleeva, A. A., Barbitoff, Y. A., Muzalevskaya, M. V., Urazgildeeva, S. A., Gurevich, V. S., Urazov, S. P., Scherbak, S. G., Sarana, A. M., Semenova, N. A., Anisimova, I. V., Guseva, D. M., Pchelina, S. N., Glotov, A. S., Zakharova, E. Y., Glotov, O. S."Identification of novel variants in the <em>LDLR</em> gene in Russian patients with familial hypercholesterolemia using targeted sequencing". Biomedical Reports 14.1 (2021): 15.
Chicago
Miroshnikova, V. V., Romanova, O. V., Ivanova, O. N., Fedyakov, M. A., Panteleeva, A. A., Barbitoff, Y. A., Muzalevskaya, M. V., Urazgildeeva, S. A., Gurevich, V. S., Urazov, S. P., Scherbak, S. G., Sarana, A. M., Semenova, N. A., Anisimova, I. V., Guseva, D. M., Pchelina, S. N., Glotov, A. S., Zakharova, E. Y., Glotov, O. S."Identification of novel variants in the <em>LDLR</em> gene in Russian patients with familial hypercholesterolemia using targeted sequencing". Biomedical Reports 14, no. 1 (2021): 15. https://doi.org/10.3892/br.2020.1391
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