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[Analysis of FBN1 gene mutations in two pedigrees affected with Marfan syndrome]
Lan Yang1, Xiaoxin Guo2, Linxin Jiang3
1School of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China; Department of Ophthalmology, Sichuan Provincial People's Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China.
Objective:
To detect mutations of fibrillin-1 (FBN1) gene in two pedigrees affected with Marfan syndrome (MFS).
Wethods:
Peripheral blood samples were collected from MFS patients and their healthy family members for extracting genomic DNA. All of the 65 exons of the FBN1 gene were analyzed by next-generation sequencing. PolyPhen-2 and SIFT was used to predict structural and functional changes in FBN1 protein.
Results:
Patients from both pedigrees presented ocular and skeletal manifestations suggestive of MFS. Two novel heterozygous mutations of the FBN1 gene, including c.1879C>T (p.R627C) in exon 16 and c.2584T>C (p.C862R) in exon 22, were identified. The same mutations were not found among unaffected members. By bioinformatic analysis, the mutations may affect the structure and function of the FBN1 protein.
Conclusion:
The c.1879C>T and c.2584T>C mutations of the FBN1 gene probably account for the disease in the two pedigrees, respectively. Identification of the c.2584T>C has enriched the spectrum of FBN1 gene mutations.
Insights
Two novel fibrillin-1 (FBN1) gene mutations, c.1879C>T and c.2584T>C, were identified in families with Marfan syndrome (MFS). These FBN1 mutations likely cause MFS by affecting protein structure and function.
Area of Science:
- Genetics
- Molecular Biology
- Medical Genetics
Background:
- Marfan syndrome (MFS) is a genetic disorder affecting connective tissue.
- Mutations in the fibrillin-1 (FBN1) gene are the primary cause of MFS.
- Identifying specific FBN1 mutations is crucial for diagnosis and understanding disease mechanisms.
Purpose of the Study:
- To detect mutations in the fibrillin-1 (FBN1) gene in two families with Marfan syndrome (MFS).
- To identify novel FBN1 mutations associated with MFS in these pedigrees.
Main Methods:
- Genomic DNA was extracted from peripheral blood samples of MFS patients and healthy relatives.
- All 65 exons of the FBN1 gene were analyzed using next-generation sequencing.
- Bioinformatic tools (PolyPhen-2, SIFT) were employed to predict the impact of identified mutations on FBN1 protein structure and function.
Main Results:
- Two novel heterozygous FBN1 mutations, c.1879C>T (p.R627C) in exon 16 and c.2584T>C (p.C862R) in exon 22, were identified in MFS patients.
- These mutations were absent in unaffected family members.
- Bioinformatic analysis suggested that these mutations may alter the structure and function of the FBN1 protein.
Conclusions:
- The identified FBN1 mutations, c.1879C>T and c.2584T>C, are likely responsible for Marfan syndrome in the studied pedigrees.
- The discovery of the c.2584T>C mutation expands the known spectrum of FBN1 gene mutations associated with MFS.
- Genetic testing for FBN1 mutations is essential for diagnosing MFS and understanding its genetic basis.
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