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The FBN1 (R2726W) mutation is not fully penetrant
S Buoni1, R Zannolli, F Macucci
1Department of Pediatrics, Obstetrics and Reproductive Medicine, Section of Pediatrics, Policlinico Le Scotte, University of Siena, Siena, Italy. zannolli@inisi.it
Annals of Human Genetics
|December 16, 2004
Summary
The R2726W mutation in the fibrillin 1 (FBN1) gene shows incomplete penetrance for Marfan syndrome features. Genetic counseling is challenging due to variable expression of this FBN1 mutation.
Area of Science:
- Genetics
- Molecular Biology
- Clinical Medicine
Background:
- The fibrillin 1 (FBN1) gene is crucial for connective tissue integrity.
- Mutations in FBN1 are associated with Marfan syndrome, a pleiotropic disorder.
- The R2726W mutation has been linked to skeletal features and tall stature.
Observation:
- A family with the FBN1 R2726W mutation was studied.
- Two affected individuals, a mother and son, carried the mutation.
- Both mutation carriers were of average height, with the son exhibiting a Marfan-like phenotype while the mother did not.
Findings:
- The FBN1 R2726W mutation demonstrates incomplete penetrance.
- Phenotypic expression of the R2726W mutation is variable, even within the same family.
- Average height was observed in individuals with the R2726W mutation, contrary to previous associations with tall stature.
Implications:
- Incomplete penetrance of the FBN1 R2726W mutation complicates accurate genetic diagnosis.
- Predicting Marfan syndrome phenotypes based solely on the R2726W mutation is unreliable.
- Genetic counseling for families with this mutation requires careful consideration of variable expressivity and reduced penetrance.