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Application of next-generation sequencing to screen for pathogenic mutations in 123 unrelated Chinese patients with Marfan syndrome or a related disease

  • Jiacheng Li
  • Chaoxia LuEmail author
  • Wei Wu
  • Yaping Liu
  • Rongrong Wang
  • Nuo Si
  • Xiaolu Meng
  • Shuyang Zhang
  • Xue ZhangEmail author
Research Paper
  • 8 Downloads

Abstract

Marfan syndrome (MFS) is a systemic connective tissue disease principally affecting the ocular, skeletal and cardiovascular systems. This autosomal dominant disorder carries a prevalence of 1:3,000 to 1:5,000. This study aims to define the mutational spectrum of MFS related genes in Chinese patients and to establish genotype-phenotype correlations in MFS. Panel-based targeted next-generation sequencing was used to analyze the FBN1, TGFBR1 and TGFBR2 genes in 123 unrelated Chinese individuals with MFS or a related disease. Genotype-phenotype correlation analyses were performed in mutation-positive patients. The results showed that 97 cases/families (78.9%; 97/123) harbor at least one (likely) pathogenic mutation, most of which were in FBN1; four patients had TGFBR1/2 mutations; and one patient harbored a SMAD3 mutation. Three patients had two FBN1 mutations, and all patients showed classical MFS phenotypes. Patients with a dominant negative-FBN1 mutation had a higher prevalence of ectopia lentis (EL). Patients carrying a haploinsufficiency-FBN1 mutation tended to have aortic dissection without EL. This study extends the spectrum of genetic backgrounds of MFS and enriches our knowledge of genotype-phenotype correlations.

Marfan syndrome FBN1 mutation next-generation sequencing genotype-phenotype correlations 

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Notes

Acknowledgements

We thank all patients and their family members who participated in this study. The study was supported by the National Natural Science Foundation of China (81400187 and 81230015), CAMS Innovation Fund for Medical Sciences (2016-I2M-1-002), the Beijing Municipal Science and Technology Commission (Z151100003915078) and the Special Research Fund for Central Public Scientific Research Institutes, Peking Union Medical College (2016ZX310160).

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Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Jiacheng Li
    • 1
  • Chaoxia Lu
    • 1
    Email author
  • Wei Wu
    • 2
  • Yaping Liu
    • 1
  • Rongrong Wang
    • 1
  • Nuo Si
    • 1
  • Xiaolu Meng
    • 1
  • Shuyang Zhang
    • 2
  • Xue Zhang
    • 1
    • 3
    Email author
  1. 1.McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical SciencesChinese Academy of Medical Science & Peking Union Medical CollegeBeijingChina
  2. 2.Department of Cardiology, Peking Union Medical College HospitalChinese Academy of Medical Science & Peking Union Medical CollegeBeijingChina
  3. 3.Laboratory of Clinical Genetics, Peking Union Medical College HospitalChinese Academy of Medical Science & Peking Union Medical CollegeBeijingChina

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