[Clinical manifestation and analysis of FBN1 gene variants in eight patients with Marfan syndrome].

OBJECTIVE

To explore the correlation between clinical manifestations and variants of fibrillin-1 (FBN1) gene in eight patients with Marfan syndrome (MFS).

METHODS

Eight patients diagnosed with MFS at Beijing Anzhen Hospital of Capital Medical University between 2016 and 2022 were selected as study subjects. Clinical data of the patients were collected. Whole-exome sequencing was carried out. Candidate variants associated with hereditary aortic aneurysm were analyzed using bioinformatics methods. Candidate pathogenic sites were verified by Sanger sequencing of patients and their family members, and rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2026088x).

RESULTS

All patients had presented with cardiovascular abnormalities, ocular abnormalities, and varying degrees of skeletal system abnormalities. Variants of the FBN1 gene (NM_000138) were found in all of them, including 3 known pathogenic variants (c.6458G>A, c.2201G>T, c.7466G>A) recorded by the ClinVar database and 5 novel variants (c.5419G>T, c.5241delC, c.1999_2003delAGAGG, c.115dupG, and c.3083-1delG). Of these, the c.3083-1delG was a mosaic variant. Based on the ACMG guidelines, three variants were classified as pathogenic, and 5 variants were classified as likely pathogenic.

CONCLUSIONS

This study has clarified the genetic basis for eight MFS patients through genetic testing. Five novel FBN1 gene variants were identified. Above findings have enriched the mutational spectrum of the FBN1 gene among Chinese MFS patients and provided a basis for the genetic counseling and clinical management.