Autosomal dominant Marfan syndrome caused by a previously reported recessive FBN1 variant

Area of Science:

• Genetics
• Cardiovascular Medicine
• Marfan Syndrome

Background:

• Pathogenic variants in the FBN1 gene are the primary cause of autosomal dominant Marfan syndrome.
• Isolated features of Marfan syndrome and autosomal recessive forms have also been linked to FBN1 variants.
• The clinical variability associated with the FBN1 variant c.1453C>T, p.(Arg485Cys) requires further investigation.

Purpose of the Study:

• To investigate the clinical spectrum associated with the specific FBN1 variant c.1453C>T, p.(Arg485Cys).
• To highlight the potential for this variant to cause autosomal dominant Marfan syndrome.
• To document cases of early-onset abdominal aortic aneurysms linked to this FBN1 variant.

Main Methods:

• Retrospective collection of clinical data from 14 individuals across two families carrying the FBN1 c.1453C>T, p.(Arg485Cys) variant.
• Diagnosis of autosomal dominant Marfan syndrome based on variant characteristics and observed phenotypes.
• Phenotypic analysis focusing on aortic pathologies.

Main Results:

• The FBN1 variant c.1453C>T, p.(Arg485Cys) was identified in two families with autosomal dominant Marfan syndrome.
• Clinical manifestations included aortic aneurysms and dissections.
• A subset of affected individuals presented with early-onset familial abdominal aortic aneurysms, indicating significant clinical variability.

Conclusions:

• The FBN1 variant c.1453C>T, p.(Arg485Cys) is confirmed as a pathogenic variant.
• This variant can lead to autosomal dominant Marfan syndrome with considerable clinical heterogeneity.
• Early-onset familial abdominal aortic aneurysms represent a potentially isolated phenotype associated with this FBN1 variant.