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Fibrillin gene (FBN1) mutations in Japanese patients with Marfan syndrome
H Chikumi1, T Yamamoto, Y Ohta
1Third Department of Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
Abstract:
Marfan syndrome (MFS; MIM #154700) is a connective tissue disorder characterized by cardiovascular, skeletal, and ocular abnormalities. The fibrillin-1 gene (FBN1; MIM no. 134797) on chromosome 15 was revealed to be the cause of Marfan syndrome. To date over 137 types of FBN1 mutations have been reported. In this study, two novel mutations and a recurrent de-novo mutation were identified in patients with MFS by means of single-strand conformational polymorphism (SSCP) analysis. The two novel mutations are a 4-bp deletion at nucleotide 2820-2823 and a G-to-T transversion at nucleotide 1421 (C474F), located on exon 23 and exon 11, respectively. A previously reported mutation at the splicing donor site of intron 2 (IVS2 G + 1A), which is predicted to cause exon skipping, was identified in a sporadic patient with classical MFS.
Insights
Researchers identified new fibrillin-1 gene mutations in patients with Marfan syndrome (MFS), a connective tissue disorder. This discovery advances understanding of MFS genetic causes and aids in diagnosing affected individuals.
Area of Science:
- Genetics
- Molecular Biology
- Medical Genetics
Background:
- Marfan syndrome (MFS) is a genetic connective tissue disorder affecting cardiovascular, skeletal, and ocular systems.
- Mutations in the fibrillin-1 gene (FBN1) are the primary cause of MFS, with over 137 mutations identified.
- Understanding FBN1 mutations is crucial for diagnosing and managing MFS.
Purpose of the Study:
- To identify novel mutations in the FBN1 gene in patients diagnosed with Marfan syndrome.
- To characterize the genetic basis of MFS in a cohort of affected individuals.
- To contribute to the growing database of FBN1 mutations associated with MFS.
Main Methods:
- Single-strand conformational polymorphism (SSCP) analysis was employed to screen for FBN1 gene mutations.
- DNA sequencing was used to confirm and characterize identified mutations.
- Genetic analysis was performed on patients with clinical diagnoses of Marfan syndrome.
Main Results:
- Two novel FBN1 mutations were identified: a 4-bp deletion (nucleotides 2820-2823) in exon 23 and a G-to-T transversion (C474F) at nucleotide 1421 in exon 11.
- A previously reported de-novo mutation (IVS2 G + 1A) in the splicing donor site of intron 2, predicted to cause exon skipping, was found in a sporadic MFS patient.
- These findings expand the spectrum of known FBN1 mutations linked to Marfan syndrome.
Conclusions:
- The study successfully identified novel and recurrent FBN1 mutations in patients with Marfan syndrome.
- These genetic findings enhance the molecular diagnosis of MFS.
- Continued genetic research is vital for a comprehensive understanding of Marfan syndrome's molecular pathology.