3 novel, not yet reported, pathogenic frameshift mutations in FBN1
were identified, which may contribute to providing diagnostic values in precision medicine of the genotype-cardiovascular phenotype relationship.
The patient was found to have a de novo heterozygous mutation in FBN1
gene p.Tyr1696Asp (Figure 1(g)).
In summary we describe the case of a 43-year-old male with a novel pathogenic variant in FBN1
causing Marfan syndrome with the rare phenotype of bilateral popliteal aneurysms.
Classic, atypically severe and neonatal Marfan syndrome: twelve mutations and genotype-phenotype correlations in FBN1
There was confirmation of an FBN1
gene mutation (exon 26, c.3143T>C).
For the present study, we chose well-known genes, regulation regions of which were often hypermethylated at colorectal cancer: SEPT9, FBN1
, VIM, SDC2, THBD, SFRP2, ESR1, TMEFF2, NGFR, ALX4, HLTF, and NEUROG1 [20,21].
In the past, the main diagnostic criteria was the Ghent's nosology (6) but according to a new diagnostic criteria as delineated by an expert group in 2010, mutations in the FBN1
gene only differentiate Marfan syndrome from the other aortic syndromes.
The genetic studies revealed no mutations in ACTA2, TGFBR1, TGFBR2, TGFB2, MYH11, MYLK, SMAD3, or FBN1
. The patient was referred to John Ritter research program in the University of Texas Medical School at Houston for additional genetic testing.
. Mutations in FBN1
have been reported in three individuals with a clinical diagnosis of Shprintzen-Goldberg syndrome (SGS).
It has been studied that these patients do not carry a mutation in the Marfan syndrome gene FBN1
encoding fibrillin 1, but instead a defect of microfibrils which are important components of the extracellular matrix associated with fibrillin.12 This has been speculated to be associated with the dural ectasias seen in SIH patients and is thought to relate to alterations in the elastin component of the dura resulting in the dilation of the dural sac due to CSF pulsation.13 Some patients have also shown to have a personal or family history of early age spontaneous retinal detachment which suggests the presence of a connective tissue disorder affecting both, the dura and the retina.
Though the variations in the gene for fibrillin-1 (FBN1
) have been shown to cause MFS, many MFS cases do not harbor any fibrillin-1 mutation suggesting that the disorder may be genetically heterogeneous.