Objective:To investigate the genetic etiology of 15 patients with suspected Marfan syndrome(MFS).Methods:Fifteen patients clinically suspected of having MFS who attended the Women and Children′s Hospital Affiliated to Qingdao University between January 2020 and August 2024 were enrolled. Amniotic fluid samples from fetuses and EDTA-anticoagulated peripheral blood samples from the patients and their family members were collected. Genomic DNA was extracted and subjected to whole exome sequencing(WES). Variants identified in positive cases were further validated by Sanger sequencing. The pathogenicity of the detected variants was assessed according to the guidelines and supplemental criteria of the American College of Medical Genetics and Genomics(ACMG).Results:All 15 patients were found to carry variants in the FBN1 gene, including 9 pathogenic variants, 5 likely pathogenic variants, and 1 variant of uncertain significance(VUS). Notably, eight novel pathogenic or likely pathogenic variants not previously reported in the literature were identified: c. 213G>C, c. 469G>T, c. 3337+ 2dup, c. 4087+ 1G>T, c. 7331_7334dup, c. 8146del, c. 8227dup, and c. 8425_8426insG. According to the revised Ghent criteria(2010), only 2 patients could be clinically diagnosed with MFS prior to WES. However, after incorporating WES-derived molecular evidence, 8 patients fulfilled the diagnostic criteria for MFS.Conclusion:The combination of WES and clinical phenotype assessment can substantially improve the diagnostic yield for MFS. Furthermore, the identification of these novel FBN1 variants expands the mutational spectrum of the gene and provides valuable evidence for future genetic counselling, prenatal diagnosis, and pathogenicity interpretation of neighboring variants.

Objective:To investigate the genetic etiology of 15 patients with suspected Marfan syndrome(MFS).Methods:Fifteen patients clinically suspected of having MFS who attended the Women and Children′s Hospital Affiliated to Qingdao University between January 2020 and August 2024 were enrolled. Amniotic fluid samples from fetuses and EDTA-anticoagulated peripheral blood samples from the patients and their family members were collected. Genomic DNA was extracted and subjected to whole exome sequencing(WES). Variants identified in positive cases were further validated by Sanger sequencing. The pathogenicity of the detected variants was assessed according to the guidelines and supplemental criteria of the American College of Medical Genetics and Genomics(ACMG).Results:All 15 patients were found to carry variants in the FBN1 gene, including 9 pathogenic variants, 5 likely pathogenic variants, and 1 variant of uncertain significance(VUS). Notably, eight novel pathogenic or likely pathogenic variants not previously reported in the literature were identified: c. 213G>C, c. 469G>T, c. 3337+ 2dup, c. 4087+ 1G>T, c. 7331_7334dup, c. 8146del, c. 8227dup, and c. 8425_8426insG. According to the revised Ghent criteria(2010), only 2 patients could be clinically diagnosed with MFS prior to WES. However, after incorporating WES-derived molecular evidence, 8 patients fulfilled the diagnostic criteria for MFS.Conclusion:The combination of WES and clinical phenotype assessment can substantially improve the diagnostic yield for MFS. Furthermore, the identification of these novel FBN1 variants expands the mutational spectrum of the gene and provides valuable evidence for future genetic counselling, prenatal diagnosis, and pathogenicity interpretation of neighboring variants.