Eight patients with Marfan syndrome were found to carry FBN1 gene variants including 3 known pathogenic variants and 5 novel variants, enriching the mutational spectrum of FBN1 among Chinese MFS patients and providing a basis for genetic counseling and clinical management.
All eight MFS patients presented with cardiovascular abnormalities, ocular abnormalities, and varying degrees of skeletal system abnormalities.
FBN1 gene variants (NM_000138) were identified in all eight patients through whole-exome sequencing.
Three known pathogenic FBN1 variants recorded in the ClinVar database were identified among the eight patients.
Five novel FBN1 gene variants not previously recorded were identified in the study cohort.
One of the novel FBN1 variants (c.3083-1delG) was identified as a mosaic variant.
This research studied eight patients diagnosed with Marfan syndrome (MFS), a genetic disorder affecting connective tissue, at a hospital in Beijing between 2016 and 2022. All eight patients showed the hallmark features of MFS, including problems with the heart and blood vessels, eyes, and skeleton. Using a comprehensive genetic testing method called whole-exome sequencing, researchers identified mutations in the FBN1 gene — the gene that produces a protein called fibrillin-1, which is essential for normal connective tissue structure — in every patient. Three of these mutations were already known to be disease-causing, while five had never been reported before. Among the five newly discovered mutations, one was particularly notable: it was a 'mosaic' variant, meaning it was only present in some of the patient's cells rather than all of them. This type of variant can be more difficult to detect and may present with variable severity. The researchers verified all variants using an additional sequencing technique (Sanger sequencing) and also tested available family members to confirm the findings. This research suggests that genetic testing can clarify the underlying cause of Marfan syndrome in individual patients and families. By identifying five previously unknown FBN1 mutations in Chinese patients, this study expands the known range of genetic changes that can cause MFS, which may help improve genetic counseling and clinical management for affected individuals and their relatives in the future.
Wu R, Sun L, Liu B, Fu X, Li X, Wang Y. (2026). [Clinical manifestation and analysis of FBN1 gene variants in eight patients with Marfan syndrome].. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics. https://doi.org/10.3760/cma.j.cn511374-20260203-00063