From the Guidelines
If you have the FBN1 gene variant c.3145G>A(p.GLY1049Ser), you should seek evaluation by a medical geneticist and cardiologist for proper diagnosis and management of Marfan syndrome, as this variant is associated with an increased risk of aortic aneurysm, dissection, and other cardiovascular complications. The FBN1 gene variant c.3145G>A (p.Gly1049Ser) is associated with Marfan syndrome, a connective tissue disorder characterized by aortic root aneurysm, aortic dissection, and other clinical features such as long bone overgrowth, arachnodactyly, and ectopia lentis 1. Regular cardiac monitoring with echocardiograms is recommended to assess your aorta, as aortic enlargement and dissection are serious complications of Marfan syndrome.
Some key considerations for management include:
- Beta-blockers such as atenolol (25-100mg daily) or losartan (50-100mg daily) may be prescribed to slow aortic growth, as recommended in the 2022 ACC/AHA guideline for the diagnosis and management of aortic disease 1
- Avoiding strenuous exercise, contact sports, and activities that involve straining or sudden changes in atmospheric pressure is crucial to prevent aortic dissection
- Annual eye examinations are important to monitor for lens dislocation and other ocular complications
- Family screening is advisable since Marfan syndrome is inherited in an autosomal dominant pattern
The specific glycine to serine substitution in the FBN1 gene variant c.3145G>A(p.GLY1049Ser) affects the calcium-binding epidermal growth factor-like domain of the fibrillin-1 protein, potentially disrupting the structural integrity of connective tissues throughout your body, including those in your cardiovascular system, skeleton, and eyes 1. It is essential to work closely with a medical geneticist and cardiologist to develop a personalized management plan and prevent complications associated with Marfan syndrome.
From the Research
FBN1 Gene Variant c.3145G>A(p.GLY1049Ser)
- The FBN1 gene encodes the protein fibrillin-1, which is essential for the formation of microfibrils in connective tissue 2.
- Mutations in the FBN1 gene, including the c.3145G>A(p.GLY1049Ser) variant, can lead to Marfan syndrome and other genetic disorders 2, 3.
- Marfan syndrome is a systemic connective tissue disorder characterized by tall stature, arachnodactyly, ectopia lentis, and thoracic aortic aneurysm and dissection 2, 3.
Genotype-Phenotype Correlation
- The correlation between FBN1 gene variants and the resulting phenotype is complex, with more than one thousand individual mutations associated with Marfan syndrome 2.
- Specific regions of the FBN1 gene can result in distinct clinical syndromes, such as Weill-Marchesani syndrome and other acromelic dysplasias 2.
- The c.3145G>A(p.GLY1049Ser) variant has not been specifically mentioned in the provided studies, but its potential impact on the phenotype can be inferred from the general understanding of FBN1 gene variants 3, 4.
Management and Treatment
- Beta-blocker therapy has been studied as a potential treatment for preventing aortic dissection in Marfan syndrome, but the evidence is limited and inconclusive 5.
- The ClinGen FBN1 variant curation expert panel (VCEP) provides guidelines for the interpretation of FBN1 gene variants, including those of uncertain significance 4.
- Early interdisciplinary medical evaluation and family genetic counseling are essential for the management of potential complications associated with FBN1 gene variants 6.