Investigation of FBN1 gene mutations in clinically diagnosed Marfan's syndrome patients’
Project no. 20050 · Status: Kapanmış (Yayın bekleniyor) · 2018
Summary
Objective: Marfan's syndrome (MFS) is an autosomal dominant type 1 fibrillinopathy that can affect eye, skeletal and cardiovascular systems. MFS is associated to have mutations in Fibrillin 1 gene (FBN1) which is located in the q21.1 locus on the long arm of chromosome 15. Revised Ghent criteria is used in the diagnosis due to high clinical heterogeneity in type 1 fibrillinopathies. Although the frequency of MFS has been reported between 1/3000- 1/10000 whereas the exact frequency is unknown due to the high clinical variation and the difficulties in the molecular diagnosis. In this study, we aimed to investigate the FBN1 gene variants and their phenotype-genotype correlations with the targeted new generation sequence analysis in 10 patients who were clinically diagnosed with MFS between January 2018 and August 2018. Materials and Methods: Ten clinically MFS diagnosed cases were selected for this study. FBN1 gene exons and exon-intron boundaries were sequenced using targeted new generation sequencing platform. Detected variants which were interpreted to be disease-causing were evaluated in terms of clinical features and phenotype-genotype correlation. Results: Disease-causing FBN1 gene variants detected in 8 of 10 cases. Identified 4 of the 8 variants were previously described (c.2585G>A, c.529T>C, c.6037+2T>C, c.1633C>T) and 4 of the 8 variants were novel mutations (c.6821G>T, c.1528_1531dup, c.7027delG, c.5077_5078insT). Genotype phenotype correlation studies about detected mutations were found to be compatible with the literature. Conclusion: This is the largest study about FBN1 mutation spectrum and phenotype-genotype correlation at MFS patients reported from the Turkish population. Furthermore, this study contribute to the literature with four novel mutations. Detection of disease-causing variants in patients with MFS will contribute to the development of diagnostic and follow-up possibilities, prevention of complications and offering prenatal and preimplantation genetic diagnosis options to families. Key Words: Marfan's syndrome; FBN1; Next-Generation Sequencing; Mutation