Genotype–phenotype correlations in Marfan syndrome

An enormous Italian pedigree of Marfan syndrome with a novel mutation in the FBN1 gene

“…Schematic depiction of mentioned locus conservation among Human, Rhesus, Mouse, Dog, Elephant, Chicken, X tropicalis, Zebrafish, and lamprey It has been reported MFS patients with a dominant-negative mutation in FBN1 are more susceptible to express ectopia lentis which argues that the evaluation of this sign is beneficial for early diagnosis of this syndrome. 9,25 Although several cohort studies have tried to make a connection between genotype and phenotype in MFS-affected individuals, the establishment of this correlation has remained unclear until now.…”

“…5,8 Most of the reported causative mutations in MFS-affected patients have been missense mutation with a dominant-negative effect which results in <35% of the expected production of fibrillin-1 protein in the extracellular matrix. 9 Splice site mutations and deletions in FBN1 are the other kinds of mutations in MFS with a lower proportion. 10 At least 25% of Marfan syndrome cases are the result of a new mutation in FBN1.…”

“…16 The correlation between genotype and phenotype in MFS is weak in many cases, and there are numerous examples of patients with a different manifestation of complication in skeletal, cardiovascular, ocular, pulmonary, and connective tissues, even in the affected families with the same type of mutations. 9,17,18 Detailed diagnostic criteria, referred to as the revised Ghent criteria, are in general use by geneticists. In the modern era, clinical criteria which were published in 1986 (Berlin) brought up to date in 1996 and revised in 2010.…”

Identification of Novel Causal FBN1 Mutations in Pedigrees of Marfan Syndrome

“…These genotypes cause severity and worse prognosis, including increased risk for aortic surgery, aortic dissection, and mortality. The genotype–phenotype effect was recognized as an important factor when making a diagnosis of MFS and later predictable phenotype severity as well as clinical decisions [ 6 , 7 ]. Some have argued that truncating may be associated with a milder disease course, which has long been questioned [ 8 , 9 ].…”

Heartbeat: The potential power of genotype–phenotype correlations

“…In an accompanying editorial, Landis, Veldtman and Ware2 summarise the pathogenesis of Marfan syndrome and discuss how this new research adds to our understanding of this condition (figure 1). They conclude: “The study detects an aortic phenotype difference based on FBN1 mutation classifications and stands as an example of the increasingly powerful capability to stratify patients based on individualised genetic testing results.…”