Early-onset Marfan Syndrome Caused by a Splicing Mutation of <i>FBN1</i> Exon 29: A Case Report

• Ogawa Yosuke

  Department of Pediatrics, The University of Tokyo

• Nakano Katsutoshi

  Department of Pediatrics, The University of Tokyo

• Shindo Takahiro

  Department of Pediatrics, The University of Tokyo

• Hirata Yoichiro

  Department of Pediatrics, The University of Tokyo

• Inuzuka Ryo

  Department of Pediatrics, The University of Tokyo

• Fujita Daishi

  Department of Cardiovascular Medicine, The University of Tokyo

• Takeda Norifumi

  Department of Cardiovascular Medicine, The University of Tokyo

• Taniguchi Yuki

  Department of Orthopedic Surgery, The University of Tokyo

• Oka Akira

  Department of Pediatrics, The University of Tokyo

Bibliographic Information

Other Title

• <i>FBN1</i>遺伝子第29番エクソンのスプライシング異常による早期発症型Marfan症候群の一例

Abstract

FBN1 mutations causing severe and early-onset Marfan syndrome (MFS) cluster in exons 24–32. Here, we report the case of a male patient with early-onset MFS who was born with arachnodactyly, annuloaortic ectasia (AAE), and aortic regurgitation (AR). At 4 years of age, he presented with progressive AAE and severe AR and was referred to our hospital. He immediately underwent David procedure. The DNA sequencing of FBN1 identified a previously reported de novo mutation in the splicing donor site of intron 29 [IVS29＋1G＞A], and transcript analyses revealed that this mutation had mediated an in-frame skipping of exon 29. Currently, the pathogenic mechanisms underlying MFS are classified as dominant-negative effect or haploinsufficiency of FBN1. However, splicing mutations can be associated with both mechanisms and require qualitative and quantitative analyses of the gene products. The severe aortic phenotype in our case appeared to be affected by the “location” (FBN1 exon 29) and the “type” of mutation (splicing mutation).

Journal

• Pediatric Cardiology and Cardiac Surgery

  Pediatric Cardiology and Cardiac Surgery 34 (2), 77-83, 2018-03-01

  Japanese Society of Pediatric Cardiology and Cardiac Surgery

Keywords

• Marfan syndrome
• <i>FBN1</i> gene
• annuloaortic ectasia
• neonatal region
• exon skipping mutation

Details

• CRID: 1390845712967314816
• NII Article ID: 130007384661
• DOI: 10.9794/jspccs.34.77
• ISSN: 21872988
• ISSN: 09111794
• Web Site: https://www.jstage.jst.go.jp/article/jspccs/34/2/34_2017-0064/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2018257247
• Text Lang: ja
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed