A familial case of Marfan syndrome: a novel variant in the FBN1 gene
- Autores: Stepanenko V.I.1, Zhalsanova I.Z.1, Fonova E.A.1, Erburova D.N.1, Gosudarkina S.N.1, Ravzhaeva E.G.1, Fadyushina S.V.1, Nikitina A.A.1, Seitova G.N.1, Klimchuk O.I.2, Stepanov V.A.1, Skryabin N.A.1
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Afiliações:
- Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
- LLC Biotech Campus
- Edição: Volume 29, Nº 4 (2025): MEDICAL GENETICS
- Páginas: 470-479
- Seção: MEDICAL GENETICS
- URL: https://bakhtiniada.ru/2313-0245/article/view/359603
- DOI: https://doi.org/10.22363/2313-0245-2025-29-4-470-479
- EDN: https://elibrary.ru/AELILG
- ID: 359603
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Texto integral
Resumo
Marfan syndrome is a hereditary connective tissue disorder characterized by marked pleiotropy and clinical variability. The main disease manifestations involve three systems: skeletal, ocular, and cardiovascular. The condition is caused by pathogenic variants in the FBN1 gene, which encodes fibrillin-1, a protein essential for the formation and maintenance of the extracellular matrix. This article describes a familial case (the proband and his father) with clinical manifestations of Marfan syndrome. Whole-genome sequencing of the proband and his father revealed a previously unreported variant, c.5782T>A, p.(Cys1928Ser), in the FBN1 gene. Thus, a molecular genetic diagnosis of Marfan syndrome was established by identifying this novel pathogenic variant. Conclusion. A confirmed diagnosis at both the clinical and molecular genetic levels in both patients determines the further therapeutic strategy and enables timely primary and secondary disease prevention within the family.
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Sobre autores
Vsevolod Stepanenko
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Autor responsável pela correspondência
Email: vsevolod.stepanenko@medgenetics.ru
ORCID ID: 0009-0004-3030-4272
Tomsk, Russian Federation
Irina Zhalsanova
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Email: vsevolod.stepanenko@medgenetics.ru
ORCID ID: 0000-0001-6848-7749
Código SPIN: 9882-3730
Tomsk, Russian Federation
Elizaveta Fonova
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Email: vsevolod.stepanenko@medgenetics.ru
ORCID ID: 0000-0002-1338-5451
Código SPIN: 5198-9456
Tomsk, Russian Federation
Daria Erburova
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Email: vsevolod.stepanenko@medgenetics.ru
ORCID ID: 0009-0004-3444-9460
Tomsk, Russian Federation
Sofia Gosudarkina
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Email: vsevolod.stepanenko@medgenetics.ru
ORCID ID: 0009-0009-6823-9441
Código SPIN: 5985-1705
Tomsk, Russian Federation
Ekaterina Ravzhaeva
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Email: vsevolod.stepanenko@medgenetics.ru
Código SPIN: 1806-8157
Tomsk, Russian Federation
Svetlana Fadyushina
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Email: vsevolod.stepanenko@medgenetics.ru
Tomsk, Russian Federation
Anastasiya Nikitina
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Email: vsevolod.stepanenko@medgenetics.ru
Tomsk, Russian Federation
Gulnara Seitova
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Email: vsevolod.stepanenko@medgenetics.ru
ORCID ID: 0000-0002-8421-1416
Código SPIN: 7393-7228
Tomsk, Russian Federation
Olesya Klimchuk
LLC Biotech Campus
Email: vsevolod.stepanenko@medgenetics.ru
Moscow, Russian Federation
Vadim Stepanov
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Email: vsevolod.stepanenko@medgenetics.ru
ORCID ID: 0000-0002-5166-331X
Código SPIN: 1893-5292
Tomsk, Russian Federation
Nikolay Skryabin
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Email: vsevolod.stepanenko@medgenetics.ru
ORCID ID: 0000-0002-2491-3141
Código SPIN: 3416-4105
Tomsk, Russian Federation
Bibliografia
- Chiu HH, Wu MH, Chen HC, Kao FY, Huang SK. Epidemiological profile of Marfan syndrome in a general population: a national database study. Mayo Clin Proc. 2014;89(1):34–42. doi: 10.1016/j.mayocp.2013.08.022
- Faivre L, Masurel-Paulet A, Collod-Béroud G, Callewaert BL, Child AH, Stheneur C, Binquet C, Gautier E, Chevallier B, Huet F, Loeys BL, Arbustini E, Mayer K, Arslan-Kirchner M, Kiotsekoglou A, Comeglio P, Grasso M, Halliday DJ, Béroud C, Bonithon-Kopp C, Claustres M, Robinson PN, Adès L, De Backer J, Coucke P, Francke U, De Paepe A, Boileau C, Jondeau G. Clinical and molecular study of 320 children with Marfan syndrome and related type I fibrillinopathies in a series of 1009 probands with pathogenic FBN1 mutations. Pediatrics. 2009;123(1):391–398. doi: 10.1542/peds.2008-0703
- Ramirez F, Dietz HC. Marfan syndrome: from molecular pathogenesis to clinical treatment. Curr Opin Genet Dev. 2007;17(3):252–258. doi: 10.1016/j.gde.2007.04.006
- Gonzales EA. Marfan syndrome. J Am Acad Nurse Pract. 2009;21(12):663–670. doi: 10.1111/j.1745-7599.2009.00461.x
- Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, Hilhorst-Hofstee Y, Jondeau G, Faivre L, Milewicz DM, Pyeritz RE, Sponseller PD, Wordsworth P, De Paepe AM. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010;47(7):476–485. doi: 10.1136/jmg.2009.072785
- Lee SS, Knott V, Jovanović J, Harlos K, Grimes JM, Choulier L, Mardon HJ, Stuart DI, Handford PA. Structure of the integrin binding fragment from fibrillin‑1 gives new insights into microfibril organization. Structure. 2004;12(4):717–729. doi: 10.1016/j.str.2004.02.023
- Jensen SA, Handford PA. New insights into the structure, assembly and biological roles of 10–12 nm connective tissue microfibrils from fibrillin‑1 studies. Biochem J. 2016;473(7):827–838. doi: 10.1042/BJ20151108
- Tiedemann K, Boraschi-Diaz I, Rajakumar I, Kaur J, Roughley P, Reinhardt DP, Komarova SV. Fibrillin‑1 directly regulates osteoclast formation and function by a dual mechanism. J Cell Sci. 2013;126(Pt 18):4187–4194. doi: 10.1242/jcs.127571
- OMIM (An Online Catalog of Human Genes and Genetic Disorders). URL: http://www.omim.org/ (Accessed 12.10.2025, Дата доступа 12.10.2025)
- Faivre L, Collod-Beroud G, Loeys BL, Child A, Binquet C, Gautier E, Callewaert B, Arbustini E, Mayer K, Arslan-Kirchner M, Kiotsekoglou A, Comeglio P, Marziliano N, Dietz HC, Halliday D, Beroud C, Bonithon-Kopp C, Claustres M, Muti C, Plauchu H, Robinson PN, Adès LC, Biggin A, Benetts B, Brett M, Holman KJ, De Backer J, Coucke P, Francke U, De Paepe A, Jondeau G, Boileau C. Effect of mutation type and location on clinical outcome in 1,013 probands with Marfan syndrome or related phenotypes and FBN1 mutations: an international study. Am J Hum Genet. 2007;81(3):454–466. doi: 10.1086/520125
- Hernándiz A, Zúñiga A, Valera F, Domingo D, Ontoria-Oviedo I, Marí JF, Román JA, Calvo I, Insa B, Gómez R, Cervera JV, Miralles M, Montero JA, Martínez-Dolz L, Sepúlveda P. Genotype FBN1/phenotype relationship in a cohort of patients with Marfan syndrome. Clin Genet. 2021;99(2):269–280. doi: 10.1111/cge.13879
- gnomAD (Genome Aggregation Database). URL: https://gnomad.broadinstitute.org/ (Accessed 12.10.2025, Дата доступа 12.10.2025)
- ClinVar. URL: https://www.ncbi.nlm.nih.gov/clinvar/ (Accessed 12.10.2025)
- REVEL (Rare Exome Variant Ensemble Learner). URL: https://sites.google.com/site/revelgenomics/ (Accessed 12.10.2025)
- The AlphaMissense Database. URL: https://alphamissense.hegelab.org/ (Accessed 12.10.2025)
- EVE (Evolutionary model of Variant Effect). URL: https://evemodel.org/ (Accessed 12.10.2025)
- Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–424. doi: 10.1038/gim.2015.30
- Ryzhkova OP, Kardymon OL, Prokhorchuk EB, Konovalov FA, Maslennikov AB, Stepanov VA, Afanasiev AA, Zaklyazminskaya EV, Rebrikov DV, Savostyanov KV, Glotov AS, Kostareva AA, Pavlov AE, Golubenko MV, Polyakov AV, Kutsev SI. Guidelines for the interpretation of human DNA sequencing data obtained by massively parallel sequencing (MPS) (2018 revision, version 2). Medical Genetics. 2019;18(2):3–23. doi: 10.25557/2073-7998.2019.02.3-23. (In Russian)
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