Detection of ten novel FBN1 mutations in Chinese patients with typical or incomplete Marfan syndrome and an overview of the genotype-phenotype correlations

Abstract Objective The aim of this study is to identify the mutation spectrum of FBN1 in patients with Marfan syndrome (MFS) or Marfan-Like Phenotypes and to analyze the genotype-phenotype correlations of existing literature. Methods and results A total of 21 unrelated patients with a definite or suspected clinical diagnosis of MFS were recruited for research. Eleven FBN1 mutations were identified in 12 patients who strictly fulfilled the Ghent criteria for MFS, and 1 FBN1 mutations were detected in 9 patients with suspected MFS by screening the mutations of FBN1 . These FBN1 mutations include 10 novel mutations (c.357 C>A, c.493 C>T, c.1374 T>A, c.4143 delG, c. 6987 C>G, c.7238 G>A, c. 7765 A>G, c.8200 A>G, c. 8431 G>A, c.8547 T>G,) and 2 previously reported mutations (c.4567 C>T, c.4615 C>T). By searching PubMed and Embase (from 1990 up to December 2018), twenty nine studies (including the present study) with 890 subjects with MFS or Marfan-like phenotypes were included to analyze the genotype-phenotype correlations. Several genotype-phenotype correlations were founded. Firstly, mutations of premature termination codons (PTC) were associated with an increased risk of major cardiovascular involvements. Secondly, the frequency of patients with major cardiovascular involvement in exons 43–65 group was as high as that in exons 24–32 group (71.4% vs. 77.0%; p  = 0.238). Finally, cysteine missense mutations might be associated with major cardiovascular involvements. Conclusions These results extended the FBN1 mutation spectrum of this rare disease and revealed the genotype-phenotype correlations in MFS by analyzing existing literature.