Understanding Missense Mutations in Fibrillin-1 and Their Impact on Marfan Syndrome
Author Information
Author(s): Yvonne Hilhorst-Hofstee, Marry EB Rijlaarsdam, Arthur JHA Scholte, Marietta Swart-van den Berg, Michel IM Versteegh, Iris van der Schoot-van Velzen, Hans-Joachim Schäbitz, Emilia K Bijlsma, Marieke J Baars, Wilhelmina S Kerstjens-Frederikse, Jacques C Giltay, Ben C Hamel, Martijn H Breuning, Gerard Pals
Primary Institution: Leiden University Medical Center
Hypothesis
How do missense mutations in the first aspartic acid of cbEGF-like domains in Fibrillin-1 affect the clinical spectrum of Marfan syndrome?
Conclusion
The study reveals that mutations in the first aspartic acid of cbEGF domains can lead to a range of phenotypes from asymptomatic to severe Marfan syndrome.
Supporting Evidence
- Nine index cases with heterozygous mutations were identified.
- A homozygous mutation was found in three family members.
- Phenotypic effects varied significantly among carriers of the same mutation.
- Clinical features were absent in heterozygous carriers in some cases.
- Previous literature supports the variability in expression of FBN1 mutations.
- Recessive inheritance was observed in a consanguineous family.
- Mutations were confirmed through DNA sequencing.
- Clinical examinations included skeletal, cardiovascular, and ophthalmological assessments.
Takeaway
Some people with a specific gene change might not show any signs of Marfan syndrome, while others can be very sick. This shows that genes can act differently in different people.
Methodology
DNA was extracted from patients and analyzed for mutations in the FBN1 gene using direct sequencing and DHPLC.
Potential Biases
Potential bias in the selection of cases and the interpretation of clinical features.
Limitations
The study may not account for all possible mutations in the FBN1 gene and their effects on phenotype.
Participant Demographics
The study included patients from a large consanguineous family and other index cases with Marfan syndrome.
Digital Object Identifier (DOI)
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