FBN1 gene mutations in 26 Hungarian patients with suspected Marfan syndrome or related fibrillinopathies

László Madar, Katalin Szakszon, György Pfliegler, Gabriella P. Szabó, Boglárka Brúgós, Natali Ronen, Judit Papp, Katalin Zahuczky, Erzsébet Szakos, G. Fekete, E. Oláh, Katalin Koczok, I. Balogh

Research output: Contribution to journalArticle

Abstract

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder mainly affecting the cardiovascular, ocular and musculo-skeletal systems. FBN1 gene mutations lead to MFS and related connective tissue disorders. In this work we described clinical and molecular data of 26 unrelated individuals with suspected MFS who were referred for FBN1 mutation analysis. FBN1 gene sequencing was performed by next generation sequencing and Sanger sequencing methods. We identified 23 causal or potentially causal (including variants of uncertain significance) FBN1 variants, seven of them was novel (˜30%). About 30% of the cases were sporadic. FBN1 mutations were associated with MFS in the majority of the patients, in two cases with severe and early onset manifestation of the syndrome. Missense mutations were detected in 69.6% (16/23), the majority of them were located in one of the cbEGF motifs and ˜70% of them substituted conserved cystein residues. Small deletions/duplications were identified in 13% of the cases (3/23), while splice site variants were detected in 17.4% (4/23). In three unrelated patients a low frequency recurrent silent variant (c.3294C > T (p.Asp1098=) was identified. FBN1 mRNA analysis showed that the mutation does not lead to aberrant splicing, based on available data the mutation was classified as benign.

Original languageEnglish
Pages (from-to)105-111
Number of pages7
JournalJournal of Biotechnology
Volume301
DOIs
Publication statusPublished - Aug 10 2019

Fingerprint

Marfan Syndrome
Genes
Musculoskeletal system
Tissue
Mutation
Connective Tissue
Messenger RNA
Missense Mutation

Keywords

  • FBN1
  • Fibrillinopathy
  • Marfan syndrome
  • Next generation sequencing
  • Silent mutation

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

FBN1 gene mutations in 26 Hungarian patients with suspected Marfan syndrome or related fibrillinopathies. / Madar, László; Szakszon, Katalin; Pfliegler, György; Szabó, Gabriella P.; Brúgós, Boglárka; Ronen, Natali; Papp, Judit; Zahuczky, Katalin; Szakos, Erzsébet; Fekete, G.; Oláh, E.; Koczok, Katalin; Balogh, I.

In: Journal of Biotechnology, Vol. 301, 10.08.2019, p. 105-111.

Research output: Contribution to journalArticle

Madar, L, Szakszon, K, Pfliegler, G, Szabó, GP, Brúgós, B, Ronen, N, Papp, J, Zahuczky, K, Szakos, E, Fekete, G, Oláh, E, Koczok, K & Balogh, I 2019, 'FBN1 gene mutations in 26 Hungarian patients with suspected Marfan syndrome or related fibrillinopathies', Journal of Biotechnology, vol. 301, pp. 105-111. https://doi.org/10.1016/j.jbiotec.2019.05.012
Madar, László ; Szakszon, Katalin ; Pfliegler, György ; Szabó, Gabriella P. ; Brúgós, Boglárka ; Ronen, Natali ; Papp, Judit ; Zahuczky, Katalin ; Szakos, Erzsébet ; Fekete, G. ; Oláh, E. ; Koczok, Katalin ; Balogh, I. / FBN1 gene mutations in 26 Hungarian patients with suspected Marfan syndrome or related fibrillinopathies. In: Journal of Biotechnology. 2019 ; Vol. 301. pp. 105-111.
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